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TY - JOUR. T1 - Mammalian ELAV-like neuronal RNA-binding proteins HuB and HuC promote neuronal development in both the central and the peripheral nervous systems. AU - Akamatsu, Wado. AU - Okano, Hirotaka J.. AU - Osumi, Noriko. AU - Inoue, Takayoshi. AU - Nakamura, Shun. AU - Sakakibara, Shin Ichi. AU - Miura, Masayuki. AU - Matsuo, Nobutake. AU - Darnell, Robert B.. AU - Okano, Hideyuki. PY - 1999/8/17. Y1 - 1999/8/17. N2 - Hu proteins are mammalian embryonic lethal abnormal visual system (ELAV)-like neuronal RNA-binding proteins that contain three RNA recognition motifs. Although Drosophila ELAV is required for the correct differentiation and survival of neurons, the roles played by the Hu genes in the mammalian nervous system remain largely unknown. To explore the in vivo functions of mouse Hu proteins, we overexpressed them in rat pheochromocytoma PC12 cells, where they induced neuronal phenotype in the absence of nerve growth factor. We have characterized the functions of various forms of ...

Nuclear RNA processing is a critical stage in eukaryotic gene expression, and is controlled in part by the expression and concentration of nuclear RNA-binding proteins. Different nuclear RNA-binding proteins are differentially expressed in different cells, helping the spliceosome to decode pre-mRNAs into alternatively spliced mRNAs. Recent post-genomic technology has exposed the complexity of nuclear RNA processing, and is starting to reveal the mechanisms and rules through which networks of RNA-binding proteins can regulate multiple parallel pathways. Identification of multiple parallel processing pathways regulated by nuclear RNA-binding proteins is leading to a systems-wide understanding of the rules and consequences of alternative nuclear RNA processing.. ...

TY - JOUR. T1 - Interaction of RNA-binding proteins HuR and AUF1 with the human ATF3 mRNA 3′-untranslated region regulates its amino acid limitation-induced stabilization. AU - Pan, Yuan Xiang. AU - Chen, Hong. AU - Kilberg, Michael S.. PY - 2005/10/14. Y1 - 2005/10/14. N2 - ATF3 expression is induced in cells exposed to a variety of stress conditions, including nutrient limitation. Here we demonstrated that the mechanism by which the ATF3 mRNA content is increased following amino acid limitation of human HepG2 hepatoma cells is mRNA stabilization. Analysis of ATF3 mRNA turnover revealed that the half-life was increased from about 1 h in control cells to greater than 8 h in the histidine-deprived state, demonstrating mRNA stabilization in response to nutrient deprivation. Treatment of HepG2 cells with thapsigargin, which causes endoplasmic reticulum stress, also increased the half-life of ATF3 mRNA. HuR is an RNA-binding protein that regulates both the stability and cytoplasmic/nuclear ...

TY - JOUR. T1 - Antitumor effects of EMAP II against pancreatic cancer through inhibition of fibronectin-dependent proliferation. AU - Schwarz, Roderich E.. AU - Awasthi, Niranjan. AU - Konduri, Srivani. AU - Caldwell, Lauren. AU - Cafasso, Danielle. AU - Schwarz, Margaret A.. N1 - Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 2010/4/15. Y1 - 2010/4/15. N2 - Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to conventional chemotherapy. The presence of both cellular and stromal fibronectin (FN) and its interaction with integrins is necessary for PDAC progression. We tested the efficacy of endothelial monocyte-activating polypeptide II (EMAP II) to inhibit PDAC progression and its ability to interfere with FN-integrin angiogenesis signaling. In heterotopic PDAC tumors EMAP II caused a significant reduction (,65%) in tumor growth, accompanied by a ,50% and 44% decrease in microvessel density and proliferative activity, respectively. EMAP II therapy caused a 62% and ...

Elucidation of the interaction of proteins with different molecules is of significance in the understanding of cellular processes. Computational methods have been developed for the prediction of protein-protein interactions. But insufficient attention has been paid to the prediction of protein-RNA interactions, which play central roles in regulating gene expression and certain RNA-mediated enzymatic processes. This work explored the use of a machine learning method, support vector machines (SVM), for the prediction of RNA-binding proteins directly from their primary sequence. Based on the knowledge of known RNA-binding and non-RNA-binding proteins, an SVM system was trained to recognize RNA-binding proteins. A total of 4011 RNA-binding and 9781 non-RNA-binding proteins was used to train and test the SVM classification system, and an independent set of 447 RNA-binding and 4881 non-RNA-binding proteins was used to evaluate the classification accuracy. Testing results using this independent ...

Mammalian gene expression patterns change profoundly in response to low oxygen levels. These changes in gene expression programs are strongly influenced by post-transcriptional mechanisms mediated by mRNA-binding factors: RNA-binding proteins (RBPs) and microRNAs (miRNAs). Here, we review the RBPs and miRNAs that modulate mRNA turnover and translation in response to hypoxic challenge. RBPs such as HuR (human antigen R), PTB (polypyrimidine tract-binding protein), heterogeneous nuclear ribonucleoproteins (hnRNPs), tristetraprolin, nucleolin, iron-response element binding proteins (IRPs), and cytoplasmic polyadenylation-element-binding proteins (CPEBs), selectively bind to numerous hypoxia-regulated transcripts and play a major role in establishing hypoxic gene expression patterns. MiRNAs including miR-210, miR-373, and miR-21 associate with hypoxia-regulated transcripts and further modulate the levels of the encoded proteins to implement the hypoxic gene expression profile. We discuss the potent

Methionyl-tRNA synthetase (MetRS) belongs to the family of 20 enzymes essential for protein biosynthesis. It links covalently methionine with its cognate tRNA. Crystal structures solved for bacterial MetRSs have given a number of interesting insights into enzyme architecture and methionylation catalysis. A comparison of sequences of MetRSs belonging to all kingdoms of life, as well as numerous biochemical and genetic studies have revealed the presence of various additional domains appended to the catalytic core of synthetase. They are responsible for interactions with tRNA and proteins. Tertiary structure of C-terminal tRNA-binding appendices can be deduced from those determined for their homologues: tRNA binding protein 111 and endothelial monocyte-activating polypeptide II. Contacts between MetRS and other proteins could be mediated not only by noncatalytic peptides but also by structural elements present in the catalytic core, e.g. Arg-Gly-Asp (RGD) motifs. Additional activities involve MetRS ...

TY - JOUR. T1 - RNPC1, an RNA-binding protein and a target of the p53 family, regulates p63 expression through mRNA stability. AU - Zhang, Jin. AU - Cho, Seong Jun. AU - Chen, Xinbin. PY - 2010/5/25. Y1 - 2010/5/25. N2 - P63, a p53 family tumor suppressor, is involved in many cellular processes, including growth suppression and differentiation. Thus, p63 activity needs to be tightly controlled. Here, we found that RNPC1, a RNA-binding protein and a target of the p53 family, regulates p63 mRNA stability and consequently p63 activity. Specifically, we showed that overexpression of RNPC1 decreases, whereas knockdown of RNPC1 increases, the half-life of p63 transcript, which leads to altered p63 expression. Consistent with this, we showed that RNPC1 binds the AU-/U-rich elements in p63 3? UTR in vitro and in vivo and the RRM domain in RNPC1 is required for binding, and regulating the stability of, p63 transcript. Furthermore, we showed that RNPC1 promotes keratinocyte differentiation by repressing ...

TY - JOUR. T1 - Hrb27C, Sqd and Otu cooperatively regulate gurken RNA localization and mediate nurse cell chromosome dispersion in Drosophila oogenesis. AU - Goodrich, Jennifer S.. AU - Clouse, K. Nicole. AU - Schüpbach, Trudi. PY - 2004/5. Y1 - 2004/5. N2 - Heterogeneous nuclear ribonucleoproteins, hnRNPs, are RNA-binding proteins that play crucial roles in controlling gene expression. In Drosophila oogenesis, the hnRNP Squid (Sqd) functions in the localization and translational regulation of gurken (grk) mRNA. We show that Sqd interacts with Hrb27C, an hnRNP previously implicated in splicing. Like sqd, hrb27C mutants lay eggs with dorsoventral defects and Hrb27C can directly bind to grk RNA. Our data demonstrate a novel role for Hrb27C in promoting grk localization. We also observe a direct physical interaction between Hrb27C and Ovarian tumor (Otu), a cytoplasmic protein implicated in RNA localization. We find that some otu alleles produce dorsalized eggs and it appears that Otu cooperates ...

TY - JOUR. T1 - Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2. AU - Long, Yicheng. AU - Bolanos, Ben. AU - Gong, Lihu. AU - Liu, Wei. AU - Goodrich, Karen J.. AU - Yang, Xin. AU - Chen, Siming. AU - Gooding, Anne R.. AU - Maegley, Karen A.. AU - Gajiwala, Ketan S.. AU - Brooun, Alexei. AU - Cech, Thomas R.. AU - Liu, Xin. N1 - Funding Information: We thank members of the Cech lab, Oncology Structural Biology and Protein Science group, and the Liu lab for useful conversations. We also thank Daniel T Youmans for technical advice and reagents for the RNA immunoprecipitation experiments. TRC is an investigator of the HHMI, which supported this research. This research was supported by Welch Foundation research grant I-1790, CPRIT research grant R1119, Rita Allen Foundation research grant, UT Southwestern Medical Center Endowed Scholar fund, and NIH grants GM114576 and GM121662 to XL XL is a W W Caruth, Jr. Scholar in Biomedical ...

TY - JOUR. T1 - Xenopus Staufen is a component of a ribonucleoprotein complex containing Vg1 RNA and kinesin. AU - Yoon, Young J.. AU - Mowry, Kimberly L.. PY - 2004/7. Y1 - 2004/7. N2 - RNA localization is a key mechanism for generating cell and developmental polarity in a wide variety of organisms. We have performed studies to investigate a role for the Xenopus homolog of the double-stranded RNA-binding protein, Staufen, in RNA localization during oogenesis. We have found that Xenopus Staufen (XStau) is present in a ribonucleoprotein complex, and associates with both a kinesin motor protein and vegetally localized RNAs Vg1 and VegT. A functional role for XStau was revealed through expression of a dominant-negative version that blocks localization of Vg1 RNA in vivo. Our results suggest a central role for XStau in RNA localization in Xenopus oocytes, and provide evidence that Staufen is a conserved link between specific mRNAs and the RNA localization machinery.. AB - RNA localization is a key ...

The mouse cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a translational regulator implicated in long-term memory maintenance. Invertebrate orthologs of CPEB3 in Aplysia and Drosophila are functional prions that are physiologically active in the aggregated state. To determine if this principle applies to the mammalian CPEB3, we expressed it in yeast and found that it forms heritable aggregates that are the hallmark of known prions. In addition, we confirm in the mouse the importance of CPEB3s prion formation for CPEB3 function. Interestingly, deletion analysis of the CPEB3 prion domain uncovered a tripartite organization: two aggregation-promoting domains surround a regulatory module that affects interaction with the actin cytoskeleton. In all, our data provide direct evidence that CPEB3 is a functional prion in the mammalian brain and underline the potential importance of an actin/CPEB3 feedback loop for the synaptic plasticity underlying the persistence of long-term memory ...

Co-Coordinator , Professor, Dept. of Molecular Genetics & Microbiology , [email protected]. Maurice Swanson is the co-coordinator of the Genetics & genomics doctoral program, and a professor in the department of molecular genetics & microbiology in the College of Medicine. Swanson works with incoming and current students, guiding them from the application process and through the doctoral program.. Swanson received his PhD from the University of California at Berkeley, followed by a postdoctoral fellowship at Northwestern University, where he studied the functions of nuclear and cytoplasmic RNA-binding proteins in RNA processing and mRNA translation. His current research is focused on the functions of repetitive DNA, particularly the roles of unstable microsatellites in RNA-mediated neurological and neuromuscular diseases.. ...

Mitochondrial RNA-binding proteins, molecular model. This complex consists of two mitochondrial RNA-binding proteins MRP1 and MRP2. These act together to bind to RNA (ribonucleic acid). Here, they here form a heteromeric complex, specifically a heterotetramer, with fourfold symmetry. These two proteins are from the protozoan Trypanosoma brucei. - Stock Image C015/4007

Mitochondrial RNA-binding proteins, molecular model. This complex consists of two mitochondrial RNA-binding proteins MRP1 and MRP2. These act together to bind to RNA (ribonucleic acid). Here, they here form a heteromeric complex, specifically a heterotetramer, with fourfold symmetry. These two proteins are from the protozoan Trypanosoma brucei. - Stock Image C015/4586

Project C1: The role of selected RNA-binding proteins and small RNAs in bacterial pathogenicity Monika Helm studied biochemistry at the Martin-Luther-University Halle-Wittenberg (2009-2014). As a PhD student Monika investigates potential roles of selected small RNAs (sRNAs) and putative RNA-binding proteins in the virulence of the plant pathogenic bacterium Xanthomonas campestris pv. vesicatoria (Xcv). Although a number of small RNAs were recently discovered in Xcv and virulence functions have been demonstrated for two of them, the targets of the other sRNAs are not known. Furthermore, the involvement of RNA-binding proteins in regulation of small RNA activity in Xcv is not well studied yet. Therefore, Monika aims at the identification and characterization of novel small RNA-binding proteins.. Supervisor: Prof. Ulla Bonas. Contact:. phone: 0345-5526296. eMail: monika.arnold(at)genetik.uni-halle.de. ...

PUFs are RNA binding proteins that promote mRNA deadenylation and decay and inhibit translation. Yeast Puf5 is the prototype for studying PUF-dependent gene repression. Puf5 binds to the Pop2 subunit of the Ccr4-Pop2-NOT mRNA deadenylase, recruiting the deadenylase and associated translational repressors to mRNAs. Here we used yeast genetics to show that Puf5 has additional roles in vivo that do not require Pop2. Deletion of PUF5 caused increased sensitivity to DNA replication stress in cells lacking Pop2, as well as in cells mutated for two activities recruited to mRNAs by the Puf5-Pop2 interaction, the deadenylase Ccr4 and the translational repressor Dhh1. A functional Puf5 RNA binding domain was required, and Puf5 cytoplasmic localisation was sufficient for resistance to replication stress, indicating posttranscriptional gene expression control is involved. In contrast to DNA replication stress, in response to the cell wall integrity pathway activator caffeine, PUF5 and POP2 acted in the same genetic

Polypyrimidine Tract Binding Protein (PTB) is an intensely studied RNA binding protein involved in several post-transcriptional regulatory events of gene expression. Initially described as a pre-mRNA splicing regulator, PTB is now widely accepted as a multifunctional protein shuttling between nucleus and cytoplasm. Accordingly, PTB can interact with selected RNA targets, structural elements and proteins. There is increasing evidence that PTB and its paralog PTBP2 play a major role as repressors of alternatively spliced exons, whose transcription is tissue-regulated. In addition to alternative splicing, PTB is involved in almost all steps of mRNA metabolism, including polyadenylation, mRNA stability and initiation of protein translation. Furthermore, it is well established that PTB recruitment in internal ribosome entry site (IRES) activates the translation of picornaviral and cellular proteins. Detailed studies of the structural properties of PTB have contributed to our understanding of the mechanism of

Human RNA-binding protein (HuR), a ubiquitously expressed member of the Hu protein family, plays an important role in mRNA degradation and has been implicated as a key post-transcriptional regulator. HuR contains three RNA-recognition motif (RRM) domains. The two N-terminal tandem RRM domains can se …

The discovery that repeat expansions in C9orf72 gene has led to many exciting discoveries in the past few years. This expansion causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and is responsible for the majority of ALS and FTD cases of European ancestry. Three, not mutually exclusive pathological mechanisms have been proposed: i) Formation of RNA foci sequestering specific RNA-binding proteins and impairing their normal function; ii) Repeat-associated non-AUG-initiated (RAN) translation of RNA repeats into toxic dipeptide repeat proteins (DPRs) and iii) haploinsufficiency resulting in reduced levels of the C9orf72 protein contributing to pathogenesis.The pathological mechanisms of C9orf72-linked disease are a very active and timely research field and many original papers and reviews are regularly published on this subject. Therefore, the goal of this Research Topic is to address the most recent progress in unraveling molecular mechanisms of C9orf72 neurodegeneration.

In this paper, we demonstrate that the RNA-binding region of eIF4GI dramatically increases the interaction between the cap structure and mammalian eIF4E. These findings appear to be at variance with those reported for yeast, in which it was concluded that a yeast eIF4G fragment lacking the RNA-binding region is capable of enhancing the cap-binding affinity of eIF4E (40). The explanations for differences in the mechanism of stimulation of eIF4E-cap interaction by eIF4G between these systems might be manifold. First, while the readout for chemical cross-linking is the interaction of eIF4E with the cap structure, the magnitude of the cross-linking is strongly dependent on the interaction of eIF4G with the RNA, so that the affinity of eIF4E for the cap is only a minor factor. The interaction between eIF4E and the cap structure is a function of equilibrium conditions, but when eIF4E is kept close to the cap, the effective concentration of eIF4E in the vicinity of the cap is greatly increased, which ...

Heme oxygenase-1 (HO-1) is an inducible rate-controlling enzyme of heme catabolism. The cytoprotective function of HO-1 activity has been verified in multiple studies, and together with its by-products is considered a key component of the cellular stress response. The transcriptional induction of HO-1 has been largely studied in response to multiple forms of stressful stimuli but our understanding of HO-1 post-transcriptional control mechanisms in neuronal cells is currently lacking. In the present report we show the involvement of the RNA-binding proteins ELAV in the regulation of HO-1 gene expression. Our study demonstrates a specific binding between HO-1 mRNA and ELAV proteins, accompanied by an increased expression of HO-1 at protein level, in a human neuroblastoma cell line treated with hemin. Clarifying the induction of HO-1 expression at post-transcriptional level may open therapeutic perspectives for treatments associated with the modulation of HO-1 expression.. ...

An RNA-binding protein that is overproduced in ovarian cancer may pres...Researchers in the UIC College of Pharmacy found that interfering with... In a previous study we observed that human ovarian tumors overexpres...In the new study Beck and research assistant professor Xiaolong He sh...The research has been published in the online version of the journal O...,RNA,splicing,factor,implicated,in,ovarian,tumor,cell,growth,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters

J.C. Schöning, et al., Reciprocal regulation of glycine-rich RNA-binding proteins via an interlocked feedback loop coupling alternative splicing to nonsense-mediated decay in Arabidopsis, Nucleic Acids Research, vol. 36, 2008, pp. 6977-6987 ...

RNA-binding proteins interact with specific RNA molecules to regulate important cellular processes. It is therefore necessary to identify the RNA interaction partners in order to understand the precise functions of such proteins. Protein-RNA interactions are typically characterized using in vivo and in vitro experiments but these may not detect all binding partners. Therefore, computational methods that capture the protein-dependent nature of such binding interactions could help to predict potential binding partners in silico. We have developed three methods to predict whether an RNA can interact with a particular RNA-binding protein using support vector machines and different features based on the sequence (the Oli method), the motif score (the OliMo method) and the secondary structure (the OliMoSS method). We applied these approaches to different experimentally-derived datasets and compared the predictions with RNAcontext and RPISeq. Oli outperformed OliMoSS and RPISeq, confirming our protein-specific

Sense and antisense transcripts of the repeat accumulate in ubiquitous small nuclear, and occasionally cytoplasmic, RNA foci. Many (G4C2) n -binding proteins have been identified that are partially sequestered by the repeat RNA. Several of the trapped RNA-binding proteins are involved in alternative splicing and splicing abnormalities have been reported in C9orf72 patients [22, 25]. However, a sophisticated study on 63 C9orf72 cases shows no correlation of sense and antisense foci with neurodegeneration or clinical parameters [6], although antisense foci have been linked to TDP-43 pathology by others [5].. Repeat-associated non-ATG (RAN) translation of both sense and antisense repeat transcripts in all reading frames generates five co-aggregating dipeptide repeat (DPR) proteins: poly-GA/GP/GR from the sense transcript and poly-GP/PA/PR from the antisense transcript. The sense-strand derived DPRs are abundant throughout the neocortex, hippocampus, thalamus and cerebellum, but scarce in brain stem ...

The selective expression of Musashi1 in stem cells or immature cells of these tissues led us to speculate that it plays a role in keeping these cells in an undifferentiated state during post-transcriptional gene regulation. We sought to identify its target RNA by using a strategy similar to that used in the study of Drosophila Musashi. By in vitro selection, we determined that the consensus ligand RNA sequence for mammalian Musashi1 is G/AU2-3(AGU). We then explored candidates for the in vivo Musashi1 target gene on the basis of the results of in vitro selection experiments as well as expression patterns and functions. We speculated that mRNAs of genes regulating neural differentiation (either positively or negatively) would be downstream targets of Musashi1 since Musashi1 is preferentially expressed in undifferentiated neuronal progenitor cells.. One of the in vivo targets of Musashi1 is m-Numb mRNA, the 3′ UTR of which has a Musashi1-binding site ( Imai et al., 2001). The m-Numb and Musashi1 ...

RNA-Binding Motif Protein 17 or Splicing factor 45 is encoded by the gene RBM17. RBM17 is a component of the spliceosome complex and displays catalytic activity during mRNA splicing. RBM17 is involved in alternative splicing, resulting in different isoforms of a gene. RBM is also thought to play a role in DNA repair (Red: Chaouki et al 2006) RBM17 is widely expressed in the nucleus and important for development. Diseases associated with this gene include sickle cell anemia and forms of Ataxia 1 ...

File:OlivasLab-Pufaction.tiff Cells respond to environmental signals and stresses by transcriptional regulation of response genes, as well as activation of more rapid post-transcriptional regulatory pathways. Modulation of mRNA degradation and translation rates is an efficient method to rapidly alter protein production in response to cellular changes. The Puf family of eukaryotic RNA-binding proteins control critical decisions in cell development and differentiation by regulating the degradation and translation of target mRNAs through interactions with 3 untranslated regions (UTRs). Pufs are also involved in cellular stress responses. Research in our lab utilizes the yeast model system Saccharomyces cerevisiae to determine how Puf proteins integrate environmental signals to alter their regulation of mRNA metabolism. For example, we have demonstrated that Puf3p responds to environmental carbon source signals to regulate the decay of nuclear-encoded transcripts that code for mitochondrial ...

This enzyme is activated during Fas-mediated apoptosis. Following Fas ligation, the enzyme, which is constitutively phosphorylated, is dephosphorylated, and it is the dephosphorylated form that causes phosphorylation of TIA-1, a nuclear RNA-binding protein. Phosphorylation of TIA-1 precedes the onset of DNA fragmentation ...

RBMY2EP (RNA binding motif protein Y-linked family 2 member E, pseudogene), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.

All of the work and power in the methodology is on the sample prep side, so hopefully you have someone great who does that for you! They validate the assay by using a human cancer cell line and identify about 1,000 RNA binding sites -- many previously characterized, and a bunch of new ones ...

Disruption of a mitochondrial RNA-binding protein gene results in decreased cytochrome b expression and a marked reduction in ubiquinol-cytochrome c reductase activity in mouse heart mitochondria ...

PMID: 14559993. SRrp86 is a unique member of the SR protein superfamily containing one RNA recognition motif and two serine-arginine (SR)-rich domains separated by an unusual glutamic acid-lysine (EK)-rich region. Previously, we showed that SRrp86 could regulate alternative splicing by both positively and negatively modulating the activity of other SR proteins and that the unique EK domain could inhibit both constitutive and alternative splicing. These functions were most consistent with the model in which SRrp86 functions by interacting with and thereby modulating the activity of target proteins. To identify the specific proteins that interact with SRrp86, we used a yeast two-hybrid library screen and immunoprecipitation coupled to mass spectrometry. We show that SRrp86 interacts with all of the core SR proteins, as well as a subset of other splicing regulatory proteins, including SAF-B, hnRNP G, YB-1, and p72. In contrast to previous results that showed activation of SRp20 by SRrp86, we now ...

We describe a novel RNA binding protein, Y14, a predominantly nuclear nucleocytoplasmic shuttling protein. Interestingly, Y14 associates preferentially with mRNAs produced by splicing but not with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Y14 associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. Splicing of a single intron is sufficient for Y14 association. Y14-containing nuclear complexes are different from general hnRNP complexes. They contain hnRNP proteins and several unique proteins including the mRNA export factor TAP. Thus, Y14 defines novel intermediates in the pathway of gene expression, postsplicing nuclear preexport mRNPs, and newly exported cytoplasmic mRNPs, whose composition is established by splicing. These findings suggest that pre-mRNA splicing imprints mRNA with a unique set of proteins that persists in the cytoplasm and thereby communicates the history of the transcript ...

FMR1 is an RNA-binding protein that is either absent or mutated in patients affected by the fragile X syndrome, the most common inherited cause of mental retardation in humans. Sequence analysis of the FMR1 protein has suggested that RNA binding is related to the presence of two K-homologous (KH) modules and an RGG box. However, no attempt has been so far made to map the RNA-binding sites along the protein sequence and to identify possible differential RNA-sequence specificity. In the present article, we describe work done to dissect FMR1 into regions with structurally and functionally distinct properties. A semirational approach was followed to identify four regions: an N-terminal stretch of 200 amino acids, the two KH regions, and a C-terminal stretch. Each region was produced as a recombinant protein, purified, and probed for its state of folding by spectroscopical techniques. Circular dichroism and NMR spectra of the N-terminus show formation of secondary structure with a strong tendency to ...

1L3K: Correlated alternative side chain conformations in the RNA-recognition motif of heterogeneous nuclear ribonucleoprotein A1.

The central dogma of biology describes the flow of genetic information from DNA to RNA to proteins. While RNA was originally believed to be a carrier of genetic information, subsequent work has shown something completely different: RNA is now known to have function independent of proteins, with a rich layer of regulatory networks. In fact, a large amount of the RNA present in a cell does not actually make proteins. This increased appreciation and understanding has led to many fascinating mechanistic insights into RNA and its role as a central player in cellular regulation and human disease.. Helping to facilitate RNA function are a large number of proteins that can bind to and regulate RNA. These RNA-binding proteins, or RBPs, number in the thousands and are made up of many different independent modular segments similar to a childs set of building blocks. In much a similar fashion, these blocks or domains provide nature with a way of mixing and matching different domains to generate new ...

Not known. Binds to RNA homopolymers, with a preference for poly(G) and poly(U) and little for poly(A) (PubMed:8760884). May bind to specific miRNA hairpins (By similarity).

p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...

Musashi Protein Powders and Supplements are well known for their Musashi Bulk, SLM, Creatine and Musashi protein bars. The Musashi brand produces supplements according to TGA standards of therapeutic goods which enables Musashi Supplements to meet world class nutrition standards. Musashi, Australias Trusted Performance Nutrition company was established in 1987. The business is named after Miyamoto Musashi, a Japanese swordsman famed for his duels and distinctive style as well as authoring The Book of Five Rings- a book on strategy, tactics, and philosophy.

TY - JOUR. T1 - Cyclin A2 is an RNA binding protein that controls Mre11 mRNA translation. AU - Kanakkanthara, Arun. AU - Jeganathan, Karthik B.. AU - Limzerwala, Jazeel F.. AU - Baker, Darren J.. AU - Hamada, Masakazu. AU - Nam, Hyun Ja. AU - Van Deursen, Willemijn H.. AU - Hamada, Naomi. AU - Naylor, Ryan M.. AU - Becker, Nicole A.. AU - Davies, Brian A.. AU - Van Ree, Janine H.. AU - Mer, Georges. AU - Shapiro, Virginia S.. AU - Maher, L. James. AU - Katzmann, David J.. AU - Van Deursen, Jan M.. N1 - Funding Information: We thank W. Zhou, M. Li, F. Jin, and X. Wang for assistance and D. Compton for providing photoactivatable GFP-tagged ?-tubulin. Supported by NIH grants CA126828 and CA168709 (J.M.v.D.) and CA166025 (L.J.M.). Publisher Copyright: © 2016, American Association for the Advancement of Science. All rights reserved.. PY - 2016/9/30. Y1 - 2016/9/30. N2 - Cyclin A2 activates the cyclin-dependent kinases Cdk1 and Cdk2 and is expressed at elevated levels from S phase until early ...

Lin28 is a conserved cytoplasmic protein with an unusual pairing of RNA-binding motifs: a cold shock domain and a pair of retroviral-type CCHC zinc fingers. In the nematode C. elegans, it is a regulator of developmental timing. In mammals, it is abundant in diverse types of undifferentiated cells. H …

In a screen for RNA-binding proteins expressed during murine spermatogenesis, we have identified a cDNA that encodes a protein of 911 amino acids that contains two copies of the double-stranded RNA-binding ...

In a screen for RNA-binding proteins expressed during murine spermatogenesis, we have identified a cDNA that encodes a protein of 911 amino acids that contains two copies of the double-stranded RNA-binding ...

TY - JOUR. T1 - The interaction between the iron-responsive element binding protein and its cognate rna is highly dependent upon both RNA sequence and structure. AU - Jaffrey, Samie R.. AU - Haile, David J.. AU - Klausner, Richard D.. AU - Harford, Joe B.. PY - 1993/9/25. Y1 - 1993/9/25. N2 - To assess the influence of RNA sequence2.urule;structure on the interaction RNAs with the iron-responsive element binding protein (IRE-BP), twenty eight altered RNAs were tested as competitors for an RNA corresponding to the ferritin H chain IRE. All changes in the loop of the predicted IRE hairpin and in the unpaired cytosine residue characteristically found in IRE stems significantly decreased the apparent affinity of the RNA for the IRE-BP. Similarly, alteration in the spacing and2.urule;or orientation of the loop and the unpaired cytosine of the stem by either increasing or decreasing the number of base pairs separating them significantly reduced efficacy as a competitor. It is inferred that the IRE-BP ...

TY - JOUR. T1 - Characterization of PfPuf2, member of the Puf family RNA-binding proteins from the malaria parasite Plasmodium falciparum. AU - Fan, Qi. AU - Li, Jinfang. AU - Kariuki, Michael. AU - Cui, Liwang. N1 - Copyright: Copyright 2018 Elsevier B.V., All rights reserved.. PY - 2004/11. Y1 - 2004/11. N2 - Puf proteins are a family of evolutionarily conserved translational regulators in eukaryotes. The malaria parasite has two Puf proteins (PfPuf1 and PfPuf2) that share 25% homology in the RNA binding domain. Here we confirmed the preferential expression of PfPuf2 in gametocyte stages using Northern analysis. The transcriptional initiation site of this gene, mapped using RNA ligase-mediated rapid amplification of cDNA end and primer extension, is located ∼300 bp upstream from the translational start codon. The 3′ end of PfPuf2 is located ∼250 bp downstream from the stop codon. The total length of the RNA is approximately 2.1 kb, consistent with the mRNA size determined by Northern ...

Interleukin-2 (IL-2) controls the proliferation of the murine T cell line B6.1 and induces transferrin receptor (TfR) mRNA steady-state levels 50-fold when added to arrested, IL-2-deprived cells. In addition, TfR mRNA is post-transcriptionally regulated by intracellular iron. Low iron levels activate a cytoplasmic RNA-binding protein, called iron regulatory factor (IRF) or iron-responsive element-binding protein, which coordinately stabilizes TfR mRNA and inhibits ferritin mRNA translation. Since ferritin expression is known to be modulated by cytokines, we decided to investigate the mechanism by which IL-2 activates TfR gene expression in B6.1 cells. Induction by IL-2 of both nuclear and cytoplasmic TfR RNA was compared with run-on transcription rates in isolated nuclei. The results revealed a 3-fold increase in TfR gene transcription and a 6-fold rise in nuclear TfR RNA reaching its steady-state level within 2 h. The main accumulation of mature mRNA in the cytoplasm occurred after 6 h in parallel with

Smaug is an RNA-binding protein that induces the degradation and represses the translation of mRNAs in the early Drosophila embryo. Smaug has two identified direct target mRNAs that it differentially regulates: nanos and Hsp83. Smaug represses the translation of nanos mRNA but has only a modest effect on its stability, whereas it destabilizes Hsp83 mRNA but has no detectable effect on Hsp83 translation. Smaug is required to destabilize more than one thousand mRNAs in the early embryo, but whether these transcripts represent direct targets of Smaug is unclear and the extent of Smaug-mediated translational repression is unknown. To gain a panoramic view of Smaug function in the early embryo, we identified mRNAs that are bound to Smaug using RNA co-immunoprecipitation followed by hybridization to DNA microarrays. We also identified mRNAs that are translationally repressed by Smaug using polysome gradients and microarrays. Comparison of the bound mRNAs to those that are translationally repressed by Smaug

Tunicates are the unique chordates to possess species reproducing sexually and asexually. Among them, the colonial ascidian Botryllus schlosseri is a reference model for the study of similarities and differences in these two developmental pathways. We here illustrate the characterization and expression pattern during both pathways of a transcript for a gene orthologous to Dazap1. Dazap1 genes encode for RNA-binding proteins and fall into the Musashi-like (Msi-like) group. Our phylogenetic analysis shows that these are related to other RNA-binding proteins (Tardbp and several heterogeneous nuclear ribonucleoproteins types) that share the same modular domain structure of conserved tandem RNA Recognition Motifs (RRMs). We also classify the whole group as derived from a single ancient duplication of the RRM. Our results also show that Dazap1 is expressed with discrete spatiotemporal pattern during embryogenesis and blastogenesis of B. schlosseri. It is never expressed in wholly differentiated tissues, but

This gene encodes a member of a family of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs), which are RNA-binding proteins that associate with pre-mRNAs in the nucleus and influence pre-mRNA processing, as well as other aspects of mRNA metabolism and transport. The protein encoded by this gene is one of the most abundant core proteins of hnRNP complexes and plays a key role in the regulation of alternative splicing. Mutations in this gene have been observed in individuals with amyotrophic lateral sclerosis 20. Multiple alternatively spliced transcript variants have been found. There are numerous pseudogenes of this gene distributed throughout the genome. [provided by RefSeq, Feb 2016 ...

TY - JOUR. T1 - The embryonic lethality of homozygous lethal yellow mice (A(y)/A(y)) is associated with the disruption of a novel RNA-binding protein. AU - Michaud, E. J.. AU - Bultman, S. J.. AU - Stubbs, L. J.. AU - Woychik, R. P.. PY - 1993/1/1. Y1 - 1993/1/1. N2 - Lethal yellow (A(y)) is a mutation at the mouse agouti (a) locus that is associated with an all-yellow coat color, obesity, diabetes, tumors in heterozygotes, and preimplantation embryonic lethality in homozygotes. Previously, we cloned and characterized the wild-type agouti gene and demonstrated that it expresses a 0.8-kb mRNA in neonatal skin. In contrast, A(y) expresses a 1.1-kb transcript that is ectopically overexpressed in all tissues examined. The A(y) mRNA is identical to the wild-type a transcript for the entire coding region, but the 5-untranslated sequence of the a gene has been replaced by novel sequence. Here, we demonstrate that the novel 5 sequence in the A(y) mRNA corresponds to the 5-untranslated sequence of ...

SR proteins are a conserved family of proteins involved in RNA splicing. SR proteins are named because they contain a protein domain with long repeats of serine and arginine amino acid residues, whose standard abbreviations are S and R respectively. SR proteins are ~200-600 amino acids in length and composed of two domains, the RNA recognition motif (RRM) region and the RS domain. SR proteins are more commonly found in the nucleus than the cytoplasm, but several SR proteins are known to shuttle between the nucleus and the cytoplasm. SR proteins were discovered in the 1990s in Drosophila and in amphibian oocytes, and later in humans. In general, metazoans appear to have SR proteins and unicellular organisms lack SR proteins. SR proteins are important in constitutive and alternative pre-mRNA splicing, mRNA export, genome stabilization, nonsense-mediated decay, and translation. SR proteins alternatively splice pre-mRNA by preferentially selecting different splice sites on the pre-mRNA strands ...

Caspases are key components of apoptotic pathways. Regulation of caspases occurs at several levels, including transcription, proteolytic processing, inhibition of enzymatic function, and protein degradation. In contrast, little is known about the extent of post-transcriptional control of caspases. Here, we describe four conserved RNA-binding proteins (RBPs)-PUF-8, MEX-3, GLD-1, and CGH-1-that sequentially repress the CED-3 caspase in distinct regions of the Caenorhabditis elegans germline. We demonstrate that GLD-1 represses ced-3 mRNA translation via two binding sites in its 3′ untranslated region (UTR), thereby ensuring a dual control of unwanted cell death: at the level of p53/CEP-1 and at the executioner caspase level. Moreover, we identified seven RBPs that regulate human caspase-3 expression and/or activation, including human PUF-8, GLD-1, and CGH-1 homologs PUM1, QKI, and DDX6. Given the presence of unusually long executioner caspase 3′ UTRs in many metazoans, translational control of ...

Zheng X, Cho S, Moon H, Loh TJ, Oh HK, Green MR, Shen H. Polypyrimidine tract binding protein inhibits IgM pre-mRNA splicing by diverting U2 snRNA base-pairing away from the branch point. RNA. 2014 Apr; 20(4):440-6 ...

A novel isoform ratio switch of the polypyrimidine tract binding proteins profile, publications, research topics, and co-authors

Selenoproteins contain the amino acid selenocysteine which is encoded by a UGA Sec codon. Recoding UGA Sec requires a complex mechanism, comprising the cis-acting SECIS RNA hairpin in the 3UTR of selenoprotein mRNAs, and trans-acting factors. Among these, the SECIS Binding Protein 2 (SBP2) is central to the mechanism. SBP2 has been so far functionally characterized only in rats and humans. In this work, we report the characterization of the Drosophila melanogaster SBP2 (dSBP2). Despite its shorter length, it retained the same selenoprotein synthesis-promoting capabilities as the mammalian counterpart. However, a major difference resides in the SECIS recognition pattern: while human SBP2 (hSBP2) binds the distinct form 1 and 2 SECIS RNAs with similar affinities, dSBP2 exhibits high affinity toward form 2 only. In addition, we report the identification of a K (lysine)-rich domain in all SBP2s, essential for SECIS and 60S ribosomal subunit binding, differing from the well-characterized L7Ae ...

Selenoproteins contain the amino acid selenocysteine which is encoded by a UGA Sec codon. Recoding UGA Sec requires a complex mechanism, comprising the cis-acting SECIS RNA hairpin in the 3′UTR of selenoprotein mRNAs, and trans-acting factors. Among these, the SECIS Binding Protein 2 (SBP2) is central to the mechanism. SBP2 has been so far functionally characterized only in rats and humans. In this work, we report the characterization of the Drosophila melanogaster SBP2 (dSBP2). Despite its shorter length, it retained the same selenoprotein synthesis-promoting capabilities as the mammalian counterpart. However, a major difference resides in the SECIS recognition pattern: while human SBP2 (hSBP2) binds the distinct form 1 and 2 SECIS RNAs with similar affinities, dSBP2 exhibits high affinity toward form 2 only. In addition, we report the identification of a K (lysine)-rich domain in all SBP2s, essential for SECIS and 60S ribosomal subunit binding, differing from the well-characterized L7Ae ...

Because previous work suggested that the fragile X protein regulates gene expression via an important group of small RNAs called microRNAs, the scientists tested whether the proteins they identified were required for a specific microRNA named bantam to function in fruit flies. The researchers performed these experiments by removing copies of the identified proteins from the fly. Instead of looking at the flies eyes, the researchers looked inside the flies using a fluorescent protein that indicates how well bantam is functioning. The investigators were surprised to find that none of the five proteins identified in the study had an effect on bantam. Even more surprisingly, neither did the fragile X mental retardation protein.. This finding and the identification of the five new proteins that interact with the fragile X mental retardation protein give new insight into additional and alternative functions of fragile X mental retardation protein. They also indicate the need for more study into ...

Aberrant regulation of gene expression in cancer is typically attributed to transcriptional control. The molecular events occurring after production of the mature mRNA molecule (posttranscriptional regulation); however, have a substantial impact on genes that fuel tumor growth (3). Our work illustrates this impact for the first time using an animal model of primary malignant glioma. We also expand the mRNA targets for HuR in cancer to include the bcl-2 family.. Expression of HuR in cancer was first described by our group in primary brain tumors but has been extensively expanded by others to include multiple tumor types (6). In normal growth and development, HuR is primarily located in the nucleus; however, in malignant tumors a cytoplasmic shift has been reported that correlates with a worse prognosis (20). Alterations in expression and subcellular localization of HuR suggest a role for posttranscriptional regulation in multiple cancer-associated pathways such as cell cycle, inflammation, ...

The Pumilio family (PUF) proteins are conserved among the eukaryotes (42). They bind to specific sequences in the 3′ untranslated region (3′UTR) of target transcripts via their conserved and characteristic PUF domain and thereby inhibit the stability or translatability of these target mRNAs (32, 50). Indeed, the PUF domain appears sufficient for PUF proteins to affect their target transcripts (32, 50). Five PUF proteins, Puf1p to Puf5p, were thought to exist in the budding yeast Saccharomyces cerevisiae (37, 49). A sixth, Puf6p, has recently been reported (9). None are essential (9, 37, 49). One of the yeast PUF proteins, Mpt5p, also known as Htr1p (23), Puf5p (37), or Uth4p (20), promotes replicative life span (3, 20, 21), the number of generations a virgin daughter cell can undergo before becoming senescent. Mpt5p is a robust regulator of ageing, since it also affects life span in a long-lived genetic background (17).. In addition to displaying a short replicative life span, mutants ...

Recently we reported that introduction of catalytically inactive PKR molecules into NIH 3T3 cells causes malignant transformation and the development of tumors in nude mice. We have proposed that PKR may be a tumor suppressor gene possibly because of its translational inhibitory properties. We have now designed and characterized a number of PKR mutants encoding proteins that retain their catalytic competence but are mutated in their regulatory double-stranded RNA (dsRNA) binding domains (RBDs). RNA binding analysis revealed that PKR proteins either lacking or with point mutations in the first RBD (RBD-1) bound negligible amounts of dsRNA activator or adenovirus VAI RNA inhibitor. Despite the lack of binding, such variants remained functionally competent but were much less active than wild-type PKR. PKR variants completely lacking RBD-1 were largely unresponsive to dsRNA in activation assays but could be activated by heparin. To complement these studies, we evaluated the effects of point ...

Davidovic L, Bechara E, Gravel M, Jaglin XH, Tremblay S, Sík A, et al. The nuclear microspherule protein 58 is a novel RNA-binding protein that interacts with fragile X mental retardation protein in polyribosomal mRNPs from neurons. Hum Mol Genet. 2006;15(9):1525-38. ...

TY - JOUR. T1 - Substrate specificities of SR proteins in constitutive splicing are determined by their RNA recognition motifs and composite pre-mRNA exonic elements. AU - Mayeda, Akila. AU - Screaton, Gavin R.. AU - Chandler, Sharon D.. AU - Fu, Xiang Dong. AU - Krainer, Adrian R.. PY - 1999/3. Y1 - 1999/3. N2 - We report striking differences in the substrate specificities of two human SR proteins, SF2/ASF and SC35, in constitutive splicing. β-Globin pre- mRNA (exons 1 and 2) is spliced indiscriminately with either SR protein. Human immunodeficiency virus tat pre-mRNA (exons 2 and 3) and immunoglobulin μ-chain (IgM) pre-mRNA (exons C3 and C4) are preferentially spliced with SF2/ASF and SC35, respectively. Using in vitro splicing with mutated or chimeric derivatives of the tat and IgM pre-mRNAs, we defined specific combinations of segments in the downstream exons, which mediate either positive or negative effects to confer SR protein specificity. A series of recombinant chimetic proteins ...

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BMC Seminar Monday, 13th of June at 10:00 in room 343.. Speaker: Miha Modic, Institute of Stem Cell Research, Helmholtz Center Munich, Neuherberg, Germany & MRC Laboratory of Molecular Biology Cambridge, Cambridge, United Kingdom.. Title: RNA BINDING PROTEIN TDP-43 SAFEGUARDS PLURIPOTENCY BY REGULATION OF DEVELOPMENTAL ALTERNATIVE POLYADENYLATION PREVENTING PARASPECKLE ASSEMBLY. Abstract: How pluripotent stem cells (PSCs) exit the self-renewing program and become committed to embryonic lineages is a fundamental question.Transcriptional, signaling and epigenetic regulation of PSC fate decisions have been the focus of research, while the understanding of RNA based mechanisms in rapid dissolvent of the self-renewing reprogramming apparatus in PSCs has been lagging behind. Recently, several studies have identified RNA-binding proteins (RBPs) as modifiers of pluripotency.Additionally, pluripotency specific pattern of alternative polyadenylation(APA) is dynamically regulated during early PSC ...

Journal of Cell Science. 2012 Apr 1;125(Pt 7):1716-1726.. Hepatic carcinoma-associated fibroblasts promote an adaptative response in colorectal cancer cells that inhibit proliferation and apoptosis: nonresistant cells die by nonapoptotic cell death.. Berdiel-Acer M, Bohem ME, López-Doriga A, Vidal A, Salazar R, Martínez-Iniesta M, Santos C, Sanjuan X, Villanueva A, Molleví DG.. Neoplasia. 2011 Oct;13(10):931-46. Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis.. Davalos V, Moutinho C, Villanueva A, Boque R, Silva P, Carneiro F, Esteller M.. Oncogene. 2011 Aug 29. Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing.. Melo S, Villanueva A, Moutinho C, Davalos V, Spizzo R, Ivan C, Rossi S, Setien F, Casanovas O, Simo-Riudalbas L, Carmona J, Carrere J, Vidal A, Aytes A, Puertas S, Ropero S, Kalluri R, Croce CM, Calin GA, Esteller ...

RBM5 (RNA-binding motif protein 5, also named H37/LUCA-15) gene from chromosome 3p21.3 has been demonstrated to be a tumor suppressor. Current researches in vitro confirm that RBM5 can suppress the growth of lung adenocarcinoma cells by inducing apoptosis. There is still no effective model in vivo, however, that thoroughly investigates the effect and molecular mechanism of RBM5 on lung adenocarcinoma. We established the transplanted tumor model on BALB/c nude mice using the A549 cell line. The mice were treated with the recombinant plasmids carried by attenuated Salmonella to induce the overexpression of RBM5 in tumor tissues. RBM5 overexpression was confirmed by immunohistochemistry staining. H&E staining was performed to observe the histological performance on plasmids-treated A549 xenografts. Apoptosis was assessed by TUNEL staining with a TUNEL detection kit. Apoptosis-regulated genes were detected by Western blot. We successful established the lung adenocarcinoma animal model in vivo. The growth of

Imai T, Tokunaga A, Yoshida T, Hashimoto M, Mikoshiba K, Weinmaster G, Nakafuku M, Okano H. 2001. The neural RNA-binding protein Musashi1 translationally regulates mammalian numb gene expression by interacting with its mRNA. Mol. Cell. Biol. 21(12):3888-900. [ PubMed ] ...

0056]Specifically, firstly, the carrier of the present invention is added to a solution containing small RNA-binding protein--small RNA complex, and the mixture is reacted at 2 to 37° C., preferably at 2 to 10° C. for 1 to 30 hours, preferably for 2 to 24 hours to form a complex of the physiologically active substance and the small RNA-binding protein--small RNA complex on the surface of the carrier of the present invention (step (1)). The above-described small RNA-binding protein--small RNA complex is the one which comprises a complex produced by binding the small RNA-binding protein involved in the present invention to the small RNA involved in the present invention, and may further comprise a protein which binds to said complex (for example, Gemin3, Gemin4, FMRP, etc.). Specific example of said complex includes, for example, RISC(RNA-induced silencing complex) and the like. The solution containing the small RNA-binding protein--small RNA complex to be used in this case includes a cell ...

A review in WIREs RNA summarizes recent work on cold-inducible RNA binding protein (CIRP) in human cancers, where it has been implicated in tumor suppression and promotion, as well as its emerging role in inflammation in human disease, including its role in cancer-related inflammation.. CIRP is expressed in a wide variety of tissues and cells and can be induced in response to cellular stress, translocating from the nucleus to the cytosol. In the cytosol, CIRP binds to target mRNAs and can increase or suppress their translation into proteins.. The function of CIRP in cancer appeared to be solely driven though its functions as an RBP that targeted cancer-associated mRNAs, but it is increasingly clear that CIRP also modulates inflammation.. Several recent studies highlight roles for CIRP in immune responses, ranging from sepsis to wound healing and tumor-promoting inflammation. CIRP functions as a modulator of inflammation in several forms of cancer as well as in other diseases.. While modulating ...

In eukaryotic cells, gene expression involves multi-step processes in the nucleus and the cytoplasm. The different processes engage specific RNA-protein complexes, RNPs. Upon activation of most, if not all genes, a precursor RNA molecule is synthesized that has to be extensively processed and modified. In addition, the RNA has to associate with a distinct set of proteins. The composition of the RNP is often dynamic and changes over time. Several RNPs are exported to the cytoplasm, where they are involved in late steps of gene expression, including the synthesis of proteins.. The aim of this thesis has been to increase our knowledge about specific steps in messenger RNP (mRNP) and ribosomal RNP (rRNP) biogenesis in the eukaryotic cell.. We have characterized a novel protein, RBD-1, that is essential for ribosome biogenesis. RBD-1 contains six RNA-binding domains and is conserved in eukaryotes. In the dipteran Chironomus tentans, RBD-1 (Ct-RBD-1) is mainly located in the nucleolus, in an RNA ...

Fox-1 homolog A, also known as ataxin 2-binding protein 1 (A2BP1) or hexaribonucleotide-binding protein 1 (HRNBP1) or RNA binding protein, fox-1 homolog (Rbfox1), is a protein that in humans is encoded by the RBFOX1 gene. Rbfox1 has an RNA recognition motif that is highly conserved among RNA-binding proteins. Rbfox1, and the related protein Rbfox2, bind the consensus RNA sequence motif (U)GCAUG within introns to exert their functions as alternative splicing factors. Additionally, the Rbfox1/A2BP1 protein binds to the C-terminus of ataxin-2, and may contribute to the restricted pathology of spinocerebellar ataxia type 2 (SCA2). Ataxin-2 is the gene product of the SCA2 gene which causes familial neurodegenerative diseases. Several alternatively spliced transcript variants have been found for this gene. Some of these variants localize to the nucleus and some other to the cytoplasm. Nuclear variants have a well-established role in tissue specific alternative splicing. Rbfox1 cytoplasmic variants ...

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BACKGROUND: Ribosomal protein S7, a crucial RNA-binding component of the ribosome, is one of two proteins that initiates assembly of the 30S ribosomal subunit. It is required for proper folding of a large 3 domain of 16S ribosomal RNA. S7 regulates its own synthesis by binding to its own mRNA. This ability of S7 to bind both messenger and ribosomal RNAs makes determination of its mode of RNA recognition particularly interesting. RESULTS: The crystal structure of S7 from Thermus thermophilus was determined by a two-wavelength anomalous diffraction experiment using the LIII edge of mercury. The S7 structure consists of a bundle of six helices and an extended beta hairpin between helices 3 and 4, with two or more RNA-binding sites on its surface. The hairpin, along with portions of helices 1, 4 and 6, forms a large, positively charged, concave surface that has the appropriate curvature and dimensions to bind double-stranded RNA. A second putative RNA-binding site comprises parts of loop 2 and the ...

microRNAs (miRNAs) are short ~22 nucleotides (nt) ribonucleic acids which post-transcriptionally regulate gene expression. miRNAs are key regulators of all cellular processes, and the correct expression of miRNAs in an organism is crucial for proper development and cellular function. As a result, the miRNA biogenesis pathway is highly regulated. In this review, we outline the basic steps of miRNA biogenesis and miRNA mediated gene regulation focusing on the role of RNA binding proteins (RBPs). We also describe multiple mechanisms that regulate the canonical miRNA pathway, which depends on a wide range of RBPs. Moreover, we hypothesise that the interaction between miRNA regulation and RBPs is potentially more widespread based on the analysis of available high-throughput datasets.

CLAVEL M., PÉLISSIER T., MONTAVON T., TSCHOPP M.A., POUCH-PÉLISSIER M.N., DESCOMBIN J., JEAN V., DUNOYER P., BOUSQUET-ANTONELLI C. and DERAGON J.M.. Evolutionary history of double-stranded RNA binding proteins in plants: identification of new cofactors involved in easiRNA biogenesis. Plant Molecular Biology, 91(26858002):131-147, 2016. ...

The S1 domain was originally identified in ribosomal protein S1 but is found in a large number of RNA-associated proteins. The structure of the S1 RNA-binding domain from the Escherichia coli polynucleotide phosphorylase has been determined using NMR methods and consists of a five-stranded antiparallel beta barrel. Conserved residues on one face of the barrel and adjacent loops form the putative RNA-binding site [ (PUBMED:9008164) ]. The structure of the S1 domain is very similar to that of cold shock proteins. This suggests that they may both be derived from an ancient nucleic acid-binding protein [ (PUBMED:9008164) ]. ...

CP001994.PE523 Location/Qualifiers FT CDS_pept 554621..555046 FT /codon_start=1 FT /transl_table=11 FT /locus_tag=Mmah_0534 FT /product=NusA family KH domain protein FT /note=COGs: COG0195 Transcription elongation factor; FT InterPro IPR004044:IPR010212; KEGG: nam:NAMH_0269 FT transcription termination factor NusA; PFAM: KH type 2 FT domain protein; SPTR: Q12WS9 NusA anti-termination factor; FT TIGRFAM: NusA family KH domain protein; PFAM: KH domain; FT TIGRFAM: NusA family KH domain protein, archaeal FT /db_xref=EnsemblGenomes-Gn:Mmah_0534 FT /db_xref=EnsemblGenomes-Tr:ADE36061 FT /db_xref=GOA:D5EA60 FT /db_xref=InterPro:IPR004044 FT /db_xref=InterPro:IPR009019 FT /db_xref=InterPro:IPR010212 FT /db_xref=InterPro:IPR015946 FT /db_xref=InterPro:IPR030842 FT /db_xref=UniProtKB/TrEMBL:D5EA60 FT /protein_id=ADE36061.1 FT /translation=MSDIKLSTDAIRYIALFESMTGAPIKDCLIDDDRIICVVNNGDMG FT AAIGKHGDNINRFKKAVDKHVDLIEYSDDPITFIKNAFGTIPTKSVEISDKNGKKVAYV FT ...

Postdoctoral positions Postdoctoral Research Associates Boyce Thompson Institute, Cornell University Ithaca, NY 2 postdoctoral positions are available to study the post-transcriptional control of chloroplast gene expression, commencing in the summer or fall of 1993. Both differential mRNA stabilities and translational control play important roles in chloroplasts, which contain RNA-binding proteins and ribonucleases that are involved in regulating RNA processing, RNA decay rates and translation initiation. In spinach, emphasis is being placed on the purification and functional analysis of sequence and/or structure-specific RNA-binding proteins (Molec. Cell. Biol 11:4380). In Chlamydomonas, transformation and genetic analyses are being used to identify translational regulatory signals. This is being accomplished by the creation of mutant translation initiation codons or 5 untranslated region deletions using chloroplast transformation, and the subsequent isolation and analysis of second-site ...

Plasmid was created in 1993 by Anne Crozat.. Crozat, A. Y., Åman, P., Mandahl, N. & Ron, D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma with t(12;16)(q13;p11). Nature 363, 640-644 (1993).. Supplied as a stab of XL-1 blue E. coli transformed with this ampicillin resistant plasmid. Predicted sequence of the plasmid in EMBL format. ...

RBM45 interactors. RBM45 monomers assemble into multimers that associate with TDP-43 via a bridging RNA. Multimers may end up in stress granules in the cytoplasm, or stress bodies in the nucleus. [Courtesy of Li et al., Scientific Reports.] What about interactions with other proteins? Li has not yet examined nuclear stress bodies but did study how RBM45 interacts with TDP-43 in the cytoplasm. The two proteins co-immunoprecipitated-but not, however, if Li treated the cells with RNase. She thinks they may bind and co-regulate the same transcripts. Because RBM45 also needed the HOA to associate with TDP-43, Li thinks RBM45 must bind RNAs as an oligomer. The researchers are now trying to identify the RNAs that bind both RBM43 and TDP-43 (Li et al., 2015).. In another recent paper, Bowser and colleagues focused on the cytoplasmic activities of RBM45. They found that like TDP-43 and FUS, it moved from the nucleus to the cytoplasm in cultured motor neurons that were undergoing oxidative stress. There, ...

Many angiogenic factors are encoded by labile transcripts bearing AU-rich elements (AREs) in their 3′-untranslated regions. These mRNA half-lives must be dynamically extended to allow significant protein production. We have demonstrated that engagement of the β2 integrin adhesion receptor, LFA-1, leads to stabilization of ARE-bearing mRNAs encoding TNF-α and IFN-γ in T lymphocytes through a required, rapid nuclear-to-cytoplasmic translocation of the RNA-binding protein HuR. We now address whether β2 integrin engagement stabilizes angiogenic factor mRNA in murine macrophages, and whether HuR is required for macrophage VEGF production at angiogenic sites in vivo. Raw 264.7 mouse macrophages and primary mouse bone marrow-derived macrophages were pretreated with PMA (1ng/ml) and allowed to adhere onto poly-L-lysine- or recombinant ICAM-1 (β2 integrin ligand)-coated dishes. RNA polymerase II (transcription) was inhibited at 3hr, after which RNA was harvested over 60 minutes for decay analysis. ...

CPEB1 overexpression lysate, 0.1 mg. Transient overexpression lysate of cytoplasmic polyadenylation element binding protein 1 (CPEB1), transcript variant 1

Gene Information This gene encodes one of four subunits of the splicing factor 3B. The protein encoded by this gene cross-links to a region in the pre-mRNA immediately upstream of the branchpoint sequence in pre-mRNA in the prespliceosomal complex A. It also may be involved in the assembly of the B C and E spliceosomal complexes. In addition to RNA-binding activity this protein interacts directly and highly specifically with subunit 2 of the splicing factor 3B. This protein contains two N-terminal RNA-recognition motifs (RRMs) consistent with the observation that it binds directly to pre-mRNA. [provided by RefSeq Jul 2008]. ...

Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5- and 3-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5-RGAAGAAC-3 (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5-CGAGGCG-3 motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors. May function as export adapter involved in mRNA nuclear export through the TAP/NXF1 pathway ...

The lack of ARE-binding by TIA-1 in HT29 cells was examined further by UV-cross-linking studies of TIA-1 with poly(A) RNA in intact cells. After exposure to UV-light, poly(A) RNA was isolated from equal numbers of HT29 and LoVo cells. The cross-linked RNA-binding proteins were separated by SDS-PAGE and TIA-1 was detected by immunoblotting. Consistent with the immunoprecipitation results, TIA-1 protein was cross-linked to mRNA in LoVo cells and there was no association of TIA-1 with mRNA in HT29 cells (Fig. 5 C). TIA-1 is known to have alternative splicing (19) which accounts for the protein doublet. The slightly higher mobility of cross-linked TIA-1 is presumably due to covalent attachment of the RNA moiety; no protein binding to mRNA was detected when UV-irradiation was omitted (unpublished data).. As LoVo cells display intact TIA-1 binding and translational repression of COX-2, we attribute loss of ARE-mediated translational regulation in HT29 cells, in part, to defects in the ability of TIA-1 ...

Neurofibrillary tangles, often referred to as tangles, are one of the characteristic brain changes in Alzheimers disease. Tangles are made from abnormal clumps of the protein tau, which normally functions as part of the cell structure and machinery to transport nutrients throughout the cell. The mechanisms that trigger the formation of tangles are not well understood. RNA (ribonucleic acid) is a long-stranded molecule that performs several functions in the cell, but one of its most prominent functions is to carry the genetic code from the genes in your DNA (deoxyribonucleic acid) to the machinery for making proteins. Several proteins bind to RNA, also known as RNA-binding proteins, some of which are responsible for making sure the RNA is folded into the right shape to make it function correctly. In some situations, such as when cells are under stress, RNA-binding proteins form clumps that store RNA for later use; these clumps are known as stress granules. Benjamin Wolozin, Ph.D., and ...

Summary. Work in my lab is focusing on understanding how microorganisms manage to rapidly adapt (and even thrive) to sudden changes in their environment. Many pathogenic species have developed very sophisticated mechanisms to efficiently scavenge essential nutrients from the host environment and even evade the immune system.. We hypothesize that this successful rapid adaptation program is underpinned by the ability of the microorganism to very rapidly remodel its gene expression profile. Obviously, transcription factors largely dictate which genes are switched on and off during adaptive responses.. However, it is becoming increasingly clear that post-transcriptional regulation plays a key role in this process by shaping gene expression profiles. Small non-coding RNAs (sRNAs) and RNA-binding proteins (RBPs) are believed to play a crucial role in post-transcriptional regulation by modulating the translation efficiency and stability of mRNA targets. However, for the vast majority their function is ...