Alternative pre-mRNA splicing in Drosophila. D. Rio - PI Alternative pre-mRNA splicing is an important mechanism for regulating gene expression in metazoans. In...
The human T-cell antigen receptor-associated T3 complex consists of at least three polypeptides, gamma, delta and epsilon. cDNA clones for the delta-chain have recently been obtained and we have used such clones to isolate the T3 delta gene. The gene has been sequenced and comprises five exons, spread over approximately 3.7 kb of DNA. Transcription of the T3 delta gene is initiated from a non-TATA promoter. S1 mapping experiments and the sequence of a novel cDNA clone show that T3 delta mRNA exists in two forms in T cells. Alternative splicing of pre-mRNA sequences corresponding to the third exon of the T3 delta gene accounts for the two species of mRNA. A putative protein, produced by translation of the shorter mRNA, would lack a transmembrane region and might be secreted or associated with the outer surface of the cell.
Alternative splicing (AS) of RNA is a key mechanism for diversification of the eukaryotic proteome. In this process, different mRNA transcripts can be produced through altered excision and/or inclusion of exons during processing of the pre-mRNA molecule. Since its discovery, AS has been shown to play roles in protein structure, function, and localization. Dysregulation of this process can result in disease phenotypes. Moreover, AS pathways are promising therapeutic targets for a number of diseases. Integral membrane proteins (MPs) represent a class of proteins that may be particularly amenable to regulation by alternative splicing because of the distinctive topological restraints associated with their folding, structure, trafficking, and function. Here, we review the impact of AS on MP form and function and the roles of AS in MP-related disorders such as Alzheimer's disease ...
Processing of accumulated pre-rRNA in Atnuc-L1 mutant plants is accurate.A) Northern blot analysis using total RNA isolated from WT and Atnuc-L1-1 mutant plants
Circular RNAs (circRNAs) are a novel group of recently discovered class of non-coding RNAs which are formed by back-splicing of pre-RNA transcript. In recent years, studies have published genome-wide circRNA-transcriptome in a number of organisms including human, cell lines, plants and animals. We have created a manually curated database, CircRNome, which is a compiled database for both animal and plants comprising predicted as well as validated cirRNAs for each organism. This serves the most updated database created for circRNAs ...
Alternative pre-mRNA splicing is a powerful mechanism that is exploited by higher eukaryotes to diversify their proteomes, and to differentially regulate the expression, function, and localization of mRNA and proteins. Pre-mRNA splicing is typically regulated by RNA-binding proteins that recognize cis-acting RNA elements, and either activate or repress splicing of adjacent exons in a temporal, and tissue specific, manner. Understanding how RNA-binding proteins control the splicing code is fundamental to understanding organismal development and disease. The SR proteins are a well-conserved class of RNA-binding proteins that have an essential role in the regulation of splice site selection, and have also been implicated as key regulators during other stages of RNA metabolism. The complexity of the RNA targets, and specificity of RNA binding location remains poorly understood for many members of the SR protein family. Here, we present a comprehensive study to elucidate how the SR proteins ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Type 1 diabetes results from the autoimmune destruction of the insulin-producing pancreatic β-cells. In addition to a major susceptibility locus in the HLA region, termed IDDM1, genetic predisposition to this disease is conferred by a locus on chromosome 11, designated IDDM2 (1). The genetic risk at IDDM2 has been attributed to the INS minisatellite (2-6), which is composed of a variable number of tandem repeat sequences. However, reanalysis of allelic association data in type 1 diabetes did not rule out intragenic variants, including a single nucleotide polymorphism (SNP) −23HphI (7), which is located in position −6 relative to the 3′ splice site of intron 1 (IVS1-6A/T). This SNP has been used as a surrogate marker for INS genotyping in a large number of studies to infer minisatellite haplotypes (class I/III) in disease susceptibility (2,3,6 and refs. therein). IVS1-6A/T is located in the polypyrimidine tract (PPT), a splicing signal of central importance for vertebrate 3′ splice site ...
DNA- and RNA binding protein, involved in several nuclear processes. Essential pre-mRNA splicing factor required early in spliceosome formation and for splicing catalytic step II, probably as a heteromer with NONO. Binds to pre-mRNA in spliceosome C complex, and specifically binds to intronic polypyrimidine tracts. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45, a phosphorylated form is sequestered by THRAP3 from the pre-mRNA in resting T-cells; T-cell activation and subsequent reduced phosphorylation is proposed to lead to release from THRAP3 allowing binding to pre-mRNA splicing regulatotry elements which represses exon inclusion. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3 side of U5 snRNA stem 1b. May be involved in a pre-mRNA coupled splicing and polyadenylation process as component of a snRNP-free complex with SNRPA/U1A. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear ...
Somatically acquired mutations in components of the RNA processing pathway in CLL. Presented is an overview illustrating the individual components of the RNA-processing pathway, with those components identified as being somatically mutated highlighted (*) and the mutated protein listed in red. Initially, nascent pre-mRNA transcripts undergo 5′ capping and binding of the cap-binding complex (CBC), followed by the formation of the major spliceosome, the machinery responsible for the removal of pre-mRNA introns via a stepwise mechanism. Initial assembly steps include formation of pre-spliceosome complex A (top left nuclear complex) involving recognition of the 5′ splice site by U1 snRNP (an interaction stabilized by members of the serine-arginine-rich (SR) protein family) and recognition of the 3′ SS region by the U2 Auxiliary factor U2AF and by U2snRNP. U2AF binds to the intronic polypyrimidine tract and 3′SS, and facilitates binding of U2 snRNP to the branch-point sequence. Stable U2 ...
Significant advances have been made in elucidating the biogenesis pathway and three-dimensional structure of the UsnRNPs, the building blocks of the spliceosome. U2 and U4/U6*U5 tri-snRNPs functionally associate with the pre-mRNA at an earlier stage of spliceosome assembly than previously thought, a …
RNA editing in the mitochondrion of Trypanosoma brucei extensively alters the adenosine triphosphate synthase (ATPase) subunit 6 precursor messenger RNA (pre-mRNA) by addition of 447 uridines and removal of 28 uridines. In vivo, the guide RNA gA6[14] is thought to specify the deletion of two uridines from the editing site closest to the 3 end. In this study, an in vitro system was developed that accurately removed uridines from this editing site in synthetic ATPase 6 pre-mRNA when gA6[14] and ATP were added. Mutations in both the guide RNA and the pre-mRNA editing site suggest that base-pairing interactions control the number of uridines deleted in vitro. Thus, guide RNAs are required for RNA editing and for the transfer of genetic information to pre-mRNAs. ...
Ohrt, T.; Odenwälder, P.; Dannenberg, J.; Prior , M.; Warkocki, Z.; Schmitzova, J.; Karaduman, R.; Gregor, I.; Enderlein, J.; Fabrizio, P. et al.; Lührmann, R.: Molecular dissection of step 2 catalysis of yeast pre-mRNA splicing investigated in a purified system. RNA 19 (7), pp. 902 - 915 (2013 ...
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During spliceosome assembly, protein-protein interactions (PPI) are sequentially formed and disrupted to accommodate the spatial requirements of pre-mRNA substrate recognition and catalysis. Splicing activators and repressors, such as SR proteins and hnRNPs, modulate spliceosome assembly and regulate alternative splicing. However, it remains unclear how they differentially interact with the core spliceosome to perform their functions. Here, we investigate the protein connectivity of SR and hnRNP proteins to the core spliceosome using probabilistic network reconstruction based on the integration of interactome and gene expression data. We validate our model by immunoprecipitation and mass spectrometry of the prototypical splicing factors SRSF1 and hnRNPA1. Network analysis reveals that a factors properties as an activator or repressor can be predicted from its overall connectivity to the rest of the spliceosome. In addition, we discover and experimentally validate PPIs between the oncoprotein SRSF1 and
Assembly of the spliceosome by the stepwise binding of the snRNPs to the pre-mRNA. In the early phase of spliceosome assembly, the U1 snRNP binds to the 5 splice site (5 SS: where exon 1 ends and the intron begins), and the U2 snRNP binds to the so-called branch point (BP: near the 3 end of the intron). This spliceosome assembly intermediate is called the A complex. The subsequent binding of the U4/U6.U5 tri snRNP complex gives rise to the precatalytic B complex. The catalytic activation of the spliceosome takes place in two steps. In the first, the RNA helicase Brr2 acts to produce the Bact complex and in the second, the RNA helicase Prp2 facilitates the formation of the B* complex. This has a functional active site and, following the recruitment of the protein Cwc25, the first step of splicing takes place. In this step, the phosphodiester bond at the 5 splice site is cleaved and, at the same time, the 5 end of the intron becomes linked to the 2 hydroxyl group of an adenosine at the ...
Rlp7 and L7 association with pre-ribosomal particles is not mutually exclusive. Extracts were prepared from cells co-expressing Rlp7-HA and L7B-TAP or, as a con
Nobel Street 3, Skolkovo Innovation Center, Moscow,. room 404. Abstract:. Eukaryotic RNAs undergo extensive processing at the. post-transcriptional level, including capping, 3-cleavage and polyadenylation, and splicing. These steps happen synergistically and, at the same time, concurrently with each other and with transcription, generating multiple alternative products arising from the same locus. We will discuss several mechanisms by which long-range complementary interactions can affect pre-mRNA splicing. Overall we find a highly non-random distribution of conserved complementary regions with respect to mammalian gene structure including not only splicing signal demarcation, but also transcriptional start and stop sites. In conjunction with NGS data this leads to a hypothesis that intramolecular RNA structure in combination with splicing could serve to suppress premature transcript polyadenylation by holding it together while the spliceosome excises the intron containing the cleavage site. ...
Developmental processes require precise spatial and temporal regulation of gene expression. Accordingly, developmental biologists have always been at the forefront of gene expression analysis, and recombinant DNA techniques such as transgenic and knockout models have greatly contributed to elucidation of developmental pathways and networks. Traditionally, these studies have focused on transcription factors and repressors that regulate the timing and strength of transcription. Recently, new regulatory mechanisms have emerged, such as post-transcriptional regulation by microRNAs and co-transcriptional regulation by alternative pre-mRNA splicing.. Alternative splicing is a pre-mRNA maturation process that consists of the removal or inclusion of certain alternative exons to produce different transcripts from one genomic locus [1, 2]. Alternative splicing is now known to be prevalent in advanced eukaryotes. In humans, recent reports show that more than 98% of multi-exonic pre-mRNAs are alternatively ...
During pre-mRNA splicing, exons in the primary transcript are precisely connected to generate an mRNA. Intron lariat RNAs are formed as by-products of this process. In addition, some exonic circular RNAs (circRNAs) may also result from exon skipping as by-products. Lariat RNAs and circRNAs are both RNase R resistant RNAs. RNase R is a strong 3 to 5 exoribonuclease, which efficiently degrades linear RNAs, such as mRNAs and rRNAs; therefore, the circular parts of lariat RNAs and the circRNAs can be segregated from eukaryotic total RNAs by their RNase R resistance. Thus, RNase R resistant RNAs could provide unexplored splicing information not available from mRNAs. Analyses of these RNAs identified repeating splicing phenomena, such as re-splicing of mature mRNAs and nested splicing. Moreover, circRNA might function as microRNA sponges. There is an enormous variety of endogenous circRNAs, which are generally synthesized in cells and tissues.
MicroRNA (miRNA), one of non-coding RNAs (ncRNAs), regulates gene expression directly by arresting the messenger RNA (mRNA) translation, which is important for identifying putative miRNAs. In this...
This gene encodes the enzyme responsible for pre-mRNA editing of the glutamate receptor subunit B by site-specific deamination of adenosines. Studies in rat found that this enzyme acted on its own pre-mRNA molecules to convert an AA dinucleotide to an AI …
Author: Maatz, H. et al.; Genre: Journal Article; Published in Print: 2014-08; Open Access; Title: RNA-binding protein RBM20 represses splicing to orchestrate cardiac pre-mRNA processing
Splicing is initiated by a productive interaction between the pre-mRNA and the U1 snRNP, in which a short RNA duplex is established between the 5 splice site ...
Burge Lab MaxEntScan::score3ss scores 23 mers using different 3ss models To score 5 splice sites go to MaxEntScan::score5ss To build your own MaxEntScan models as described in the paper (below) refer to MaxEntScan::build Reference ...
The adenovirus major late transcription unit (MLTU) is an example of a complex alternatively spliced gene, in which more than 15 different 3 splice sites can be joined to a common 5 splice site. Maturation of the full repertoire of possible mRNAs requires late viral protein synthesis and occurs only at late stages of the infectious cycle (16-24 hpi). We are trying to decipher the mechanisms regulating alternative 3 splice site choice during the infectious cycle. Therefore, we examined the splicing activity of several 3 splice sites from the MLTU in vitro in nuclear extracts prepared from adenovirus infected cells (Ad NE) and from uninfected cells. The results suggest that pre-mRNAs with "weak" 3 splice sites (short, atypical polypyrimidine tracts) are activated and pre-mRNAs with long, prototypical polypyrimidine tracts are repressed in Ad NE. In fact, our data show a reciprocal correlation between the strength of a polypyrimidine tract, defined by its affinity for U2AF65K in vitro, and the ...
The current model of spliceosome assembly was developed principally from the in vitro pattern of small nuclear ribonucleoprotein (snRNP) particle association with synthetic splicing substrates (reviewed in Moore et al., 1993; Madhani and Guthrie, 1994; Krämer, 1996). In mammals and yeast, spliceosome assembly progresses by the sequential addition of the U1 snRNP→U2 snRNP→U4/U6.U5 tri‐snRNP particles to the pre‐mRNA. Before 5′ splice‐site cleavage (chemical step I in splicing), the affinities of the U1 and U4 snRNAs for the splicing complex are greatly reduced and, under many (Pikielny et al., 1986; Cheng and Abelson, 1987; Konarska and Sharp, 1987) although not all (Blencowe et al., 1989) isolation conditions, the U4 snRNA is lost from the spliceosome. This model of spliceosome assembly is supported by the abridged spliceosome assembly profiles observed when splicing is inhibited by specific mutations in the pre‐mRNA or when one of the many trans‐acting components of splicing is ...
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 ...
The Let-7 microRNA precursor was identified from a study of developmental timing in C. elegans, and was later shown to be part of a much larger class of non-coding RNAs termed microRNAs. miR-98 microRNA precursor from human is a let-7 family member. Let-7 miRNAs have now been predicted or experimentally confirmed in a wide range of species (MIPF0000002). miRNAs are initially transcribed in long transcripts (up to several hundred nucleotides) called primary miRNAs (pri-miRNAs), which are processed in the nucleus by Drosha and Pasha to hairpin structures of about 70 nucleotide. These precursors (pre-miRNAs) are exported to the cytoplasm by exportin5, where they are subsequently processed by the enzyme Dicer to a ~22 nucleotide mature miRNA. The involvement of Dicer in miRNA processing demonstrates a relationship with the phenomenon of RNA interference. In human genome, the cluster let-7a-1/let-7f-1/let-7d is inside the region B at 9q22.3, with the defining marker D9S280-D9S1809. One minimal LOH ...
Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5- and 3-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2,3-cyclic phosphate and 5-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. Isoform 1 probably carries the active site for 5-splice site cleavage. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3-end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events. Isoform 2 is responsible for processing a yet unknown RNA substrate. ...
MicroRNAs (miRNAs) regulate cardiovascular biology and disease, but the role of flow-sensitive microRNAs in atherosclerosis is still unclear. Here we identify miRNA-712 (miR-712) as a mechanosensitive miRNA upregulated by disturbed flow (d-flow) in endothelial cells, in vitro and in vivo. We also show that miR-712 is derived from an unexpected source, pre-ribosomal RNA, in an exoribonuclease-dependent but DiGeorge syndrome critical region 8 (DGCR8)-independent manner, suggesting that it is an atypical miRNA. Mechanistically, d-flow-induced miR-712 downregulates tissue inhibitor of metalloproteinase 3 (TIMP3) expression, which in turn activates the downstream matrix metalloproteinases (MMPs) and a disintegrin and metalloproteases (ADAMs) and stimulate pro-atherogenic responses, endothelial inflammation and permeability. Furthermore, silencing miR-712 by anti-miR-712 rescues TIMP3 expression and prevents atherosclerosis in murine models of atherosclerosis. Finally, we report that human miR-205 ...
Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest. Using a combined pooled-genome wide shRNA library screen and global proteomic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in breast cancer cells. Notably, JA induced significant tumor-specific cell death and a significant increase in unspliced pre-mRNAs. In contrast, depletion of endogenous SF3B1 ...
Cleavage and polyadenylation specificity factor (CPSF) is relevant to the cleavage of the 3′ signaling region from a newly synthesized pre-messenger RNA (pre-mRNA) molecule. Specifically, it is in the process…. Read More Read More. ...
Excision, or splicing, of noncoding regions (introns) from precursor (pre)-mRNA in eukaryotes is catalyzed by the spliceosome, a ribonucleoprotein complex comprising recyclable small nuclear (sn)RNA and protein components. An early step in assembly of th
Pre-miR miRNA Precursor Molecules ... MicroRNAs (miRNAs) are small regulatory RNAs...,Precursor,miRNAs,for,Successful,miRNA,Functional,Studies,biological,advanced biology technology,biology laboratory technology,biology device technology,latest biology technology
RNA-binding protein that acts as a regulator of alternative pre-mRNA splicing. Involved in apoptotic cell death through the regulation of the apoptotic factor BCL2L1 isoform expression. Modulates the ratio of proapoptotic BCL2L1 isoform S to antiapoptotic BCL2L1 isoform L mRNA expression. When overexpressed, stimulates proapoptotic BCL2L1 isoform S 5-splice site (5-ss) selection, whereas its depletion caused the accumulation of antiapoptotic BCL2L1 isoform L. Promotes BCL2L1 isoform S 5-ss usage through the 5-CGGGCA-3 RNA sequence. Its association with LUC7L3 promotes U1 snRNP binding to a weak 5 ss in a 5-CGGGCA-3-dependent manner. Binds to the exonic splicing enhancer 5-CGGGCA-3 RNA sequence located within exon 2 of the BCL2L1 pre-mRNA. Also involved in the generation of an abnormal and truncated splice form of SCN5A in heart failure.
Over three decades ago, Birchler (1979) studied the expression of several enzymes in a dosage series of the long arm of chromosome 1 in maize. Some of the gene products that were not encoded on this chromosome arm were negatively correlated in amount with the dosage of the chromosome arm. The range of effect was within the limits of an inverse correlation, and hence, this effect became known as the "inverse effect." Subsequent studies on protein profiles in different dosage series of maize indicated that any one protein could be modulated in this way by several regions of the genome (Birchler and Newton 1981). Any one region would modulate some fraction of the total detectable proteins. In addition to inverse effects, there were also direct correlations of protein levels that operated in trans (i.e. variation of a particular chromosome arm would modulate the expression of a protein encoded elsewhere in the genome). Different chromosome arms produced a few to many effects. Further studies ...
The removal of introns from pre-mRNA transcripts is an essential step in the expression of almost all human genes. we are collaborating with several groups to d...
tRNase Z is an essential endonuclease responsible for tRNA 3-end maturation. tRNase Z exists in a short form (tRNase ZS) and a long form (tRNase ZL). Prokaryotes have only tRNase ZS,whereas eukaryotes can have both forms of tRNase Z.
Burge, C. B., Tuschl, T. and Sharp, P.A. Splicing of precursors to mRNAs by the spliceosomes. In RNA World II, R. Gesteland, T. Cech, and J. Atkins, eds., Cold Spring Harbor Laboratory Press, NY, pp. 525-560 (1999) Dredge BK, Polydorides AD, Darnell RB. The splice of life: alternative splicing and neurological disease. Nat Rev Neurosci. 2001 Jan;2(1):43-50. Hastings ML, Krainer AR. Pre-mRNA splicing in the new millennium. Curr Opin Cell Biol. 2001 Jun;13(3):302-9. Maniatis T, Reed R. An extensive network of coupling among gene expression machines. Nature. 2002 Apr 4;416(6880):499-506. Nilsen, T.W. RNA/RNA interactions in nuclear pre-mRNA splicing. In: RNA Structure and Function. R. Simons and M. Grunberg-Manago eds., Cold Spring Harbor Laboratory Press, NY, pp. 279-307 (1998). Staley JP, Guthrie C. Mechanical devices of the spliceosome: motors, clocks, springs, and things. Cell. 1998 Feb 6;92(3):315-26. Tollervey D, Caceres JF. RNA processing marches on. Cell. 2000 Nov 22;103(5):703-9. ...
mirnaDetect :: DESCRIPTION A java based mining tool mirnaDetect is developed for detect potential pre-miRNAs from the genome-scale data. This program is based both on search and machine learning algorithms. ::DEVE
tRNase Z is an essential endonuclease responsible for tRNA 3-end maturation. tRNase Z exists in a short form (tRNase Z(S)) and a long form (tRNase Z(L)). Prokaryotes have only tRNase Z(S), whereas eukaryotes can have both forms of tRNase Z. Most eukaryotes characterized thus far, including Saccharo …
A complex secondary structure in U1A pre-mRNA that binds two molecules of U1A protein is required for regulation of polyadenylation.: The human U1A protein-U1A
SF3B4 is one of four subunits of the splicing factor 3B. The protein cross-links to a region in the pre-mRNA immediately upstream of the branchpoint…
Mikronizuotas L-Glutaminas su Glutamino peptidais. Glutaminas - viena iš dvidešimties pagrindinių amino rūgščių, kurios organizme yra daugiausiai - net 64% . Glutaminas detoksikuoja amoniaką, reguliuoja proteino sintezę ir protein
The interactions established at the 5-splice site during spliceosome assembly are likely to be important for both precise recognition of the upstream intron boundary and for positioning this site in the active center of the spliceosome. Definition of the RNA-RNA and the RNA-protein interactions at the 5 splice site would be facilitated by the use of a small substrate amenable to modification during chemical synthesis. We describe a trans-splicing reaction performed in Saccharomyces cerevisiae extracts in which the 5 splice site and the 3 splice site are on separate molecules. The RNA contributing the 5 splice site is only 20 nucleotides long and was synthesized chemically. The trans-splicing reaction is accurate and has the same sequence, ATP, and Mg^2+ requirements as cis-splicing. We also report how deoxy substitutions around the 5-splice site affect trans-splicing efficiency. ...
Pre-mRNA splicing is executed by the spliceosome, which has eight major functional states each with distinct composition. Five of these eight human spliceosomal complexes, all preceding exon ligation, have been structurally characterized. In this study, we report the cryo-electron microscopy structures of the human post-catalytic spliceosome (P complex) and intron lariat spliceosome (ILS) at average resolutions of 3.0 and 2.9 Å, respectively. In the P complex, the ligated exon remains anchored to loop I of U5 small nuclear RNA, and the 3-splice site is recognized by the junction between the 5-splice site and the branch point sequence. The ATPase/helicase Prp22, along with the ligated exon and eight other proteins, are dissociated in the P-to-ILS transition. Intriguingly, the ILS complex exists in two distinct conformations, one with the ATPase/helicase Prp43 and one without. Comparison of these three late-stage human spliceosomes reveals mechanistic insights into exon release and spliceosome ...
Pre-mRNA splicing takes place in an RNA machine known as the spliceosome, which consists of small nuclear ribonucleoprotein particles (snRNPs)1 and non-snRNP protein factors. The RNA components in the spliceosome form the catalytic core through a series of dynamic RNA-RNA interactions which are likely to be mediated and/or stabilized by non-snRNP protein factors (for recent reviews see Nilsen, 1998; Staley and Guthrie, 1998). Among the best characterized non-snRNP splicing factors are SR proteins which contain one or two RNA recognition motifs and a signature RS domain containing multiple serine and arginine repeats (for reviews see Fu, 1995; Manley and Tacke, 1996). The RNA recognition motifs bind to RNA sequences in a coordinated fashion to determine splicing specificity (Chandler et al., 1997) and commit pre-mRNA substrates to the splicing pathway (Fu, 1993), whereas the RS domains mediate specific protein- protein interactions in a number of spliceosomal assembly steps (Wu and Maniatis, ...
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 ...
Lucero Rogel. PREP Program. Lab Group: Alan Zahler. PREP Research: The Zahler lab works to investigate the mechanism of RNA splicing by utilizing C. elegans as a model organism. Accurate splicing of pre-mRNA is a critical step in the gene expression pathway in eukaryotes carried out by a large ribonucleoprotein complex known as the spliceosome. The spliceosome consists of 5 RNAs (U1, U2, U4, U5, and U6) that assemble onto the pre-mRNA by recognizing conserved sequence elements that define the beginning and ends of introns, known as 5 and 3 splice sites. To facilitate the interactions between the pre-mRNA and the 5 RNAs, over 150 proteins are employed to aid in the process. Currently in the lab, I am working on elucidating the role of spliceosomal protein SNRP-27 in 5 splice site selection by uncovering differential interactions that a mutant and wild type form of this factor have with the splicing machinery.. Undergraduate Major: Biochemistry and Molecular Biology. Undergraduate Institution: ...