RNA-Binding Protein FUS

RNA-Binding Proteins

RNA

Molecular Sequence Data

Ribonucleoproteins

RNA, Messenger

Heterogeneous-Nuclear Ribonucleoproteins

Poly(A)-Binding Proteins

RNA, Viral

Hu Paraneoplastic Encephalomyelitis Antigens

Amino Acid Sequence

RNA Splicing

Base Sequence

RNA Stability

Protein Binding

RNA, Small Interfering

RNA, Double-Stranded

RNA Editing

Binding Sites

Nuclear Factor 90 Proteins

RNA Processing, Post-Transcriptional

RNA-binding protein FUS

Genetics of amyotrophic lateral sclerosis

Elizabeth Fisher (neuroscientist)

Neuroepigenetics

Extraskeletal myxoid chondrosarcoma

FAM208b

Proteinopathy

ERG (gene)

TAF15

FET protein family

Hippocampal sclerosis

Fus

SMCO3

ISLR

Drosha

RNA-binding protein EWS

DNA damage-inducible transcript 3

Myxoid liposarcoma

ILF3

HNRNPR

KIAA2013

List of MeSH codes (D12.776)

FUSIP1

TAR DNA-binding protein 43

Zinc finger protein 226

U1 spliceosomal RNA

PURA

List of MeSH codes (D12.776.157)

RNA recognition motif

Transportin 1

Sarcoma10

• RNA-binding protein FUS/TLS (FUsed in Sarcoma/Translocated in LipoSarcoma), also known as heterogeneous nuclear ribonucleoprotein P2 is a protein that in humans is encoded by the FUS gene. (wikipedia.org)
• FUS gene rearrangement has been implicated in the pathogenesis of myxoid liposarcoma, low-grade fibromyxoid sarcoma, Ewing sarcoma, and a wide range of other malignant and benign tumors (see FET protein family). (wikipedia.org)
• Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma ( FUS ) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. (uky.edu)
• The RNA sequence of the vaccine as well as the spike protein target interaction were analyzed for the potential to convert intracellular RNA binding proteins TAR DNA binding protein (TDP-43) and Fused in Sarcoma (FUS) into their pathologic prion conformations. (shtfplan.com)
• Fused in sarcoma (FUS) is a DNA/RNA binding protein that is dysfunctional in various malignant tumors. (biomedcentral.com)
• Many SG proteins are affected by mutations causative of these conditions, including fused in sarcoma (FUS). (worktribe.com)
• A neuropathological subtype of FTD, frontotemporal lobar degeneration (FTLD)-FET, is characterized by protein aggregates consisting of the RNA-binding protein fused in sarcoma (FUS). (ulaval.ca)
• Immunohistochemical findings prompted us to sequence the fused in sarcoma (FUS) gene. (ox.ac.uk)
• ¹⁵ Globally, the most common include expansions of chromosome 9 open reading frame 72 (C9orf72) and variants in superoxide dismutase 1 (SOD1), TANK1-binding kinase 1, fused in sarcoma (FUS), and TAR DNA-binding protein 43 (TDP-43). (aviadobio.com)
• Among them, FUST-1, the homolog of FUS (fused in sarcoma), down-regulates both circRNA formation and exon skipping of the same pre-mRNA without affecting its cognate linear mRNA levels. (oist.jp)

Aggregates6

• Such FUS aggregates are a pathological hallmark of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). (wikipedia.org)
• As a result, FUS protein and mRNA are trapped within cells and likely form clumps (aggregates), which have been found in nerve cells that control muscle movement (motor neurons) in some people with ALS. (medlineplus.gov)
• It is unclear if protein aggregates cause the nerve cell death that leads to ALS. (medlineplus.gov)
• [10] Furthermore, evidence has emerged that small, non-fibrillar protein aggregates known as oligomers are toxic to the cells of an affected organ, and that amyloidogenic proteins in their fibrillar form may be relatively benign. (wikipedia.org)
• TDP-43 pathology includes cytoplasmic aggregates of the normally nuclear protein. (alzforum.org)
• Different methodologies were used to examine whether these drugs can aid removal of FUS aggregates and decrease levels of mutant FUS protein. (edu.au)

Frontotemporal lobar degene3

• The disease entities which are now considered subtypes of FTLD-FUS are atypical frontotemporal lobar degeneration with ubiquitinated inclusions (aFTLD-U), NIFID, and basophilic inclusion body disease (BIBD), which together with ALS-FUS comprise the FUS-proteopathies. (wikipedia.org)
• For example, cystic fibrosis is caused by a defective cystic fibrosis transmembrane conductance regulator (CFTR) protein, [3] and in amyotrophic lateral sclerosis / frontotemporal lobar degeneration (FTLD), certain gene-regulating proteins inappropriately aggregate in the cytoplasm, and thus are unable to perform their normal tasks within the nucleus. (wikipedia.org)
• The molecular genetic relationship with frontotemporal lobar degeneration with FUS pathology remains to be clarified. (ox.ac.uk)

Inclusions17

• Subsequently, FUS has also emerged as a significant disease protein in a subgroup of frontotemporal dementias (FTDs), previously characterized by immunoreactivity of the inclusion bodies for ubiquitin, but not for TDP-43 or tau with a proportion of the inclusions also containing alpha-internexin (α-internexin) in a further subgroup known as neuronal intermediate filament inclusion disease (NIFID). (wikipedia.org)
• Phase transition also contributes to the formation of cytoplasmic inclusions found in the cell bodies of FUS ALS patients motor neurons. (uky.edu)
• The nature of these inclusions has remained elusive, as the proteins localized to them have not been identified. (uky.edu)
• Additionally, the functional consequence of the accumulation of cytoplasmic FUS inclusions has not been established, nor is it understood how they contribute to selective motor neuron death. (uky.edu)
• We carried out two related, but independent studies to characterize the proteins that may be included in FUS-positive inclusions. (uky.edu)
• Immunofluorescent staining of proteins interacting with mutant FUS were localized to cytoplasmic inclusions. (uky.edu)
• In the second study, we developed a protocol to isolate dynamic FUS inclusions and employed LC MS/MS to identify all proteins associated with FUS inclusions. (uky.edu)
• We identified a cohort of proteins involved in translation, splicing, and RNA export to be associated with the FUS inclusions. (uky.edu)
• Many proteins found in pathological inclusions are known to undergo liquid-liquid phase separation, a reversible process of molecular self-assembly. (nih.gov)
• The authors report that TDP-43 possesses a prion-like domain that allows it to bind polyglutamate inclusions, such as those found in Huntington disease. (alzforum.org)
• Validation experiments for a mFA-specific protein, hnRNPA3, confirmed its RNA-dependent interaction with FUS and its sequestration into FUS inclusions in cultured cells and in a FUS transgenic mouse model. (worktribe.com)
• Juvenile ALS with basophilic inclusions is a FUS proteinopathy with FUS mutations. (ox.ac.uk)
• BACKGROUND: Juvenile amyotrophic lateral sclerosis (ALS) with basophilic inclusions is a form of ALS characterized by protein deposits in motor neurons that are morphologically and tinctorially distinct from those of classic sporadic ALS. (ox.ac.uk)
• METHODS: We identified neuropathologically 4 patients with juvenile ALS with basophilic inclusions and tested the hypothesis that specific RNA binding protein pathology may define this type of ALS. (ox.ac.uk)
• Basophilic inclusions were strongly positive for FUS protein but negative for TAR DNA binding protein 43 (TDP-43). (ox.ac.uk)
• CONCLUSION: Juvenile ALS with basophilic inclusions is a FUS proteinopathy and should be classified as ALS-FUS. (ox.ac.uk)
• Although FUS/TLS is normally located predominantly in the nucleus, the pathogenic mutant forms of FUS/TLS traffic to, and form inclusions in, the cytoplasm of affected spinal motor neurons or glia. (cornell.edu)

MRNA13

• FUS/TLS was independently identified as the hnRNP P2 protein, a subunit of a complex involved in the maturation of pre-mRNA. (wikipedia.org)
• Additionally, FUS/TLS has been found to bind a relatively long region in the 3′ untranslated region (UTR) of the actin-stabilising protein Nd1-L mRNA, suggesting that rather than recognising specific short sequences, FUS/TLS interacts with multiple RNA-binding motifs or recognises secondary conformations. (wikipedia.org)
• The FUS protein is also involved in processing molecules called messenger RNA (mRNA), which serve as the genetic blueprints for making proteins. (medlineplus.gov)
• By cutting and rearranging mRNA molecules in different ways, the FUS protein controls the production of different versions of certain proteins. (medlineplus.gov)
• Once the FUS protein processes the mRNA, it transports the mRNA out of the nucleus where it gets taken up by other cell structures to be further processed into a mature protein. (medlineplus.gov)
• Most of these mutations change single protein building blocks in the FUS protein and often affect the region of the protein involved in DNA binding and mRNA processing. (medlineplus.gov)
• He was one of the first researchers to discover ribosomal frameshifting as a gene expression mechanism in plant RNA viruses and to demonstrate recombination between transgene mRNA and genomic RNA of an infecting virus. (bio5.org)
• This protein belongs to the FET family of RNA-binding proteins which have been implicated in cellular processes that include regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. (sitoolsbiotech.com)
• Furthermore, we found that proteasome subunits and certain nucleocytoplasmic transport factors are depleted from mFAs, whereas translation elongation, mRNA surveillance and splicing factors as well as mitochondrial proteins are enriched in mFAs, as compared to SGs. (worktribe.com)
• In recent years, nucleic acid therapy involving various types of ribonucleic acids (RNAs), including messenger RNA (mRNA), small interfering RNA (siRNA), and microRNA (miRNA), has rapidly emerged as a new cornerstone of modern medicine. (techadda2.com)
• In the present context of successful mRNA drugs, the further synthesis of linear mRNA into circular RNA (circRNA) through end-to-end connections to enhance mRNA stability and prolong protein translation time has emerged as a new hot topic in the field of mRNA therapy. (techadda2.com)
• Naturally occurring circular RNAs in organisms mostly arise from precursor mRNAs (pre-mRNA) through a process known as back-splicing. (techadda2.com)
• We then examined the effects of a loss of FUS function on NCDN in neurons and found that depleting cells of FUS leads to a decrease in NCDN protein and mRNA levels. (ulaval.ca)

Polymerase7

• It also associates with the general transcriptional machinery and may influence transcription initiation and promoter selection by interacting with RNA polymerase II and the TFIID complex. (wikipedia.org)
• Mutations in the FUS nuclear localization sequence impairs the poly (ADP-ribose) polymerase (PARP)-dependent DNA damage response. (wikipedia.org)
• This reaction requires a DNA template, reaction buffer, and bacteriophage RNA polymerase. (techadda2.com)
• Bacteriophage RNA polymerases are commonly derived from T7, SP6, or T3 phages, with T7 RNA polymerase being the more prevalent choice. (techadda2.com)
• The proteins, based on similarity to other coronaviruses, include the papain-like proteinase protein (NSP3), 3C-like proteinase (NSP5), RNA-dependent RNA polymerase (NSP12, RdRp), helicase (NSP13, HEL), endoRNAse (NSP15), 2'-O-Ribose-Methyltransferase (NSP16) and other nonstructural proteins. (micrornaprofile.com)
• The RNA-dependent RNA polymerase is a target of antiviral therapies. (micrornaprofile.com)
• 2023) RNA polymerase II-associated proteins reveal pathways affected in VCP-related amyotrophic lateral sclerosis. (ulelab.info)

Mutations14

• In 2009 two separate research groups analysed 26 unrelated families who presented with a type6 ALS phenotype, and found 14 mutations in the FUS gene. (wikipedia.org)
• At least 85 mutations in the FUS gene have been found to cause amyotrophic lateral sclerosis (ALS), a condition characterized by progressive muscle weakness, a loss of muscle mass, and an inability to control movement. (medlineplus.gov)
• People with ALS caused by mutations in the FUS gene tend to develop the disease at a younger age and have a decreased life expectancy compared with individuals who have sporadic ALS or ALS caused by mutations in other genes. (medlineplus.gov)
• Rarely, people with ALS caused by FUS gene mutations also develop a condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. (medlineplus.gov)
• It is unclear why some people with FUS gene mutations develop FTD and others do not. (medlineplus.gov)
• Specific mutations involving the FUS gene are involved in several types of cancer. (medlineplus.gov)
• FUS gene mutations have also been found in myxoid liposarcomas, which occur in fatty tissues of the body, and in cancer of the blood-forming cells in the bone marrow called acute myeloid leukemia (AML). (medlineplus.gov)
• ALS mutations in TLS/FUS disrupt target gene expression. (medlineplus.gov)
• By contrast, in the case of TEM-1 beta-lactamase mutations, aggregation is linked to a decreased cell fitness due to inactivation of protein function. (frontiersin.org)
• Protein domain analysis indicates that the carboxyl-terminus of FUS/TLS, where most of the ALS-associated mutations are clustered, is required but not sufficient for the toxicity of the protein. (cornell.edu)
• To date, two-thirds of fALS are associated with mutations in any of more than 25 genes [ 3 , 4 , 5 ], encoding proteins involved in protein homeostasis, RNA metabolism, vesicular trafficking, and cytoskeletal organization. (en-journal.org)
• The FUS protein is a nuclear DNA/RNA binding protein that regulates gene expression and that when mutations occur in this protein it can aggregate and contribute to MND pathology. (edu.au)
• When two mutations (R446S and P447L), which are equivalent to natural mutations in the FUS nuclear localization signal (R524S and P525L) observed in amyotrophic lateral sclerosis, were introduced into FUST-1, both of the mutations dramatically down-regulated the formation of circRNAs. (oist.jp)
• The ability to accurately detect nucleotide regions that differentially react with RNA structure probing reagents under diverse conditions, or due to the effect of mutations, is of great importance to researchers. (biomedcentral.com)

Cytoplasmic10

• Moreover, a positive relationship was found between nuclear and cytoplasmic co-localization FUS and IL-13Rα2 expression. (biomedcentral.com)
• In HGG, IL-13Rα2 combined with nuclear and cytoplasmic co-localization of FUS was associated with worse OS. (biomedcentral.com)
• IL-13Rα2 expression was significantly associated with cytoplasmic distribution of FUS in human glioma samples and could be the independent prognostic factors for OS, while the prognostic value of its co-expression with cytoplasmic FUS in glioma need to be addressed in the future studies. (biomedcentral.com)
• Formation of cytoplasmic RNA-protein structures called stress granules (SGs) is a highly conserved cellular response to stress. (worktribe.com)
• Mutant FUS variants have high affinity to SGs and also spontaneously form de novo cytoplasmic RNA granules. (worktribe.com)
• Results of our study support a pathogenic role for cytoplasmic FUS assemblies in ALS-FUS. (worktribe.com)
• We examined the effects of NCDN haploinsufficiency on FUS and found that depleting primary cortical neurons of NCDN causes a reduction in the total number of FUS-positive cytoplasmic granules. (ulaval.ca)
• Moreover, we provide evidence for a negative feedback loop of toxicity between NCDN and FUS, where loss of NCDN alters FUS cytoplasmic dynamics, which in turn has an impact on NCDN expression. (ulaval.ca)
• Here we report a yeast model of human FUS/TLS expression that recapitulates multiple salient features of the pathology of the disease-causing mutant proteins, including nuclear to cytoplasmic translocation, inclusion formation, and cytotoxicity. (cornell.edu)
• A genome-wide genetic screen using a yeast over-expression library identified five yeast DNA/RNA binding proteins, encoded by the yeast genes ECM32, NAM8, SBP1, SKO1, and VHR1, that rescue the toxicity of human FUS/TLS without changing its expression level, cytoplasmic translocation, or inclusion formation. (cornell.edu)

Metabolism5

• FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. (uky.edu)
• To understand how protein synthesis is suppressed by mutant FUS mediated defects in RNA metabolism, we examined changes in a well conserved RNA turnover pathway namely: nonsense mediated decay (NMD). (uky.edu)
• TDP-43 regulates RNA metabolism, trafficking, and localization of thousands of target genes. (nature.com)
• 2022). Sexually dimorphic RNA helicases DDX3X and DDX3Y differentially regulate RNA metabolism through phase separation. (upenn.edu)
• 2023) A computationally-enhanced hiCLIP atlas reveals Staufen1-RNA binding features and links 3' UTR structure to RNA metabolism. (ulelab.info)

Affinity6

• Consistently, in vitro studies have shown that FUS/TLS binds RNA, single-stranded DNA and (with lower affinity) double-stranded DNA. (wikipedia.org)
• In this first study, we utilized immunoprecipitation of wild-type and mutant FUS in the presence and absence of RNase, followed by LC MS/MS. The identified proteins represent those that directly or indirectly interact with FUS, with relatively high affinity that can be pulled down with immunoprecipitation. (uky.edu)
• Because CaM can bind with high affinity to a relatively small alpha-helical region of many proteins, success in clearly defining the essential elements of CaM binding motifs seems feasible and should provide a means of identifying CaM binding proteins. (embl.de)
• However, when the researchers performed the same experiments with the TDP-43 mutants Q331K and M337V, they found that much more FUS tagged along, suggesting the mutants have increased affinity for FUS, or a for complex that also contains FUS. (alzforum.org)
• Here we used affinity purification to isolate mFAs and physiological SGs and compare their protein composition. (worktribe.com)
• Recombinant protein was captured through anti-DDK affinity column followed by conventional chromatography steps. (origene.com)

Cytoplasm3

• The interaction is most likely an early event" in disease, Ling speculated, leading up to later stages where TDP-43 and FUS, normally nuclear proteins, are mislocalized and aggregated in the cytoplasm. (alzforum.org)
• These circular RNAs are distributed in the cytoplasm and exhibit half-lives ranging from 18.8-23.7 hours, significantly longer than their linear homologs which have half-lives of only 4.0-7.4 hours. (techadda2.com)
• Granular and compact FUS deposits were identified in glia and neuronal cytoplasm and nuclei. (ox.ac.uk)

Interaction8

• The function of FUS in the DNA damage response in neurons involves a direct interaction with histone deacetylase 1 (HDAC1). (wikipedia.org)
• Their interaction with FUS varied greatly in their requirements for RNA. (uky.edu)
• RNAct: Protein-RNA interaction predictions for model organisms with supporting experimental data. (tartaglialab.com)
• Calmodulin (CaM) is recognized as a major calcium sensor and orchestrator of regulatory events through its interaction with a diverse group of cellular proteins. (embl.de)
• Many investigations have focused on defining the region of interaction between CaM and its cellular targets and the action of CaM on target protein function. (embl.de)
• Three recognition motifs for CaM interaction are discussed in the context of experimental investigations of a variety of CaM target proteins. (embl.de)
• Researchers have long sought to connect TDP-43 and FUS in a common pathway leading to neurodegenerative disease, so Ling and colleagues pursued this particular interaction further. (alzforum.org)
• Both have prion-like, protein-protein interaction domains, he noted, by which they could potentially join the same complex. (alzforum.org)

Neurodegeneration3

• This impairment leads to neurodegeneration and FUS aggregate formation. (wikipedia.org)
• Emerging evidence supports the hypothesis that aberrant phase separation behavior may serve as a trigger of protein aggregation in neurodegeneration, and efforts to understand and control the underlying mechanisms are underway. (nih.gov)
• 2015. Human C9ORF72 hexanucleotide expansion reproduces RNA foci and dipeptide repeat proteins but not neurodegeneration in BAC transgenic mice . (cardiff.ac.uk)

Highly conserved2

• FUS/TLS, EWS and TAF15 have a similar structure, characterised by an N-terminal QGSY-rich region, a highly conserved RNA recognition motif (RRM), multiple RGG repeats, which are extensively demethylated at arginine residues and a C-terminal zinc finger motif. (wikipedia.org)
• TDP-43 is a highly conserved, ubiquitously expressed, multifunctional nucleic acid-binding protein composed of two RNA recognition motifs (RRM), nuclear localization (NLS) and export signals (NES), and a carboxy-terminal glycine rich region. (nature.com)

Mutant9

• Protein translation assays using both N2A and ALS patient fibroblasts demonstrated suppression of protein biosynthesis in mutant FUS expressing cells. (uky.edu)
• We found that NMD is hyperactivated in cells expressing mutant FUS, likely due to chronic suppression of protein translation shifting the pathways autoregulatory circuit to allow for hyperactivation. (uky.edu)
• We concluded that mutant FUS suppresses protein biosynthesis and disrupts NMD regulation. (uky.edu)
• Indeed, the network inference problem persists in systems biology, despite an abundance of regulatory evidence in the form of TF binding experiments, genetic screens for candidate nodes, and mutant expression profiling experiments. (biomedcentral.com)
• Ling and colleagues wondered if the mutant proteins hang around in the cell longer than the wild-type does. (alzforum.org)
• Mutant FUS-containing assemblies (mFAs), often called "pathological SGs", are proposed to play a role in ALS-FUS pathogenesis. (worktribe.com)
• In conclusion, we show that SG-like structures formed by mutant FUS are structurally distinct from SGs, prone to persistence, likely cannot functionally replace SGs, and affect a spectrum of cellular pathways in stressed cells. (worktribe.com)
• To assess the pathogenic effects of this variant, we have used patient-derived skin fibroblasts and motor neuron-specific overexpression of the RAPGEF2-E1357K mutant protein in Drosophila . (en-journal.org)
• This project aimed to test the effect of treating transgenic zebrafish larvae expressing mutant FUS-R521C-GFP protein with drugs that induce the autophagy pathway. (edu.au)

Pathology3

• 15:10 Professor Peter Giese, Do deficits in synaptic protein synthesis underlie pathology and memory loss in Alzheimer's disease? (ukdri.ac.uk)
• FUS pathology. (uni-muenchen.de)
• The goal of this study was to identify genetic variants contributing to FTLD-FET and to investigate their effects on FUS pathology. (ulaval.ca)

Oncogene1

• The name FUS refers to the fact that genetic recombination events result in fusion oncogene proteins (ONCOGENE PROTEINS, FUSION) that contain the N-terminal region of this protein. (bvsalud.org)

Nucleic acid-binding1

• FUS/TLS is a nucleic acid binding protein that, when mutated, can cause a subset of familial amyotrophic lateral sclerosis (fALS). (cornell.edu)

Neurons6

• FUS loss-of-function results in increased DNA damage in neurons. (wikipedia.org)
• Ling plans to examine TDP-43 stability and protein-protein interactions in neurons and patient-derived cells. (alzforum.org)
• It investigated the role of the RNA-binding protein FUS in the degeneration and death of motor neurons. (gatescambridge.org)
• Normally the FUS protein exists in lipid droplets, but in patients with inherited motor neurone disease it forms abnormal masses which are detrimental to neurons. (gatescambridge.org)
• Recently, new evidence suggests that PIWI proteins and piRNAs also play important roles in various somatic tissues, including neurons. (molcells.org)
• Through the large-scale isolation of neurons from the first larval stage of Caenorhabditis elegans, C. elegans neuronal circRNA profile was analyzed for the first time by RNA sequencing of the whole-transcriptome. (oist.jp)

HnRNP2

• This gene encodes a multifunctional protein component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex. (sitoolsbiotech.com)
• TDP-43 is known to modify mRNAs, so it was no surprise to see components of the heterogenous nuclear ribonuclear (hnRNP) protein complex, as well as other RNA-binding proteins. (alzforum.org)

Vitro6

• however, using in vitro selection (SELEX), a common GGUG motif has been identified in approximately half of the RNA sequences bound by FUS/TLS. (wikipedia.org)
• FUS/TLS has also been proposed to bind human telomeric RNA (UUAGGG)4 and single-stranded human telomeric DNA in vitro. (wikipedia.org)
• FUS undergoes liquid- liquid phase transition in vitro , allowing for its participation in stress granules and RNA transport granules. (uky.edu)
• PKC phosphorylation of these proteins also inhibits their binding to RNA in vitro. (embl.de)
• Although the majority of natural circular RNAs are non-coding RNAs, meaning they cannot be translated into proteins, research has shown that artificially synthesized circular RNAs with internal ribosome entry site (IRES) sequences can be translated both in vivo and in vitro. (techadda2.com)
• Enzymatic ligation for circular RNA synthesis is typically achieved through in vitro transcription (IVT) reactions. (techadda2.com)

Genes2

• Recently, FUS/TLS was also shown to repress the transcription of RNAP III genes and to co-immunoprecipitate with TBP and the TFIIIB complex. (wikipedia.org)
• The FUS protein attaches (binds) to DNA and regulates an activity called transcription, which is the first step in the production of proteins from genes. (medlineplus.gov)

Ribosomal2

• The identified non-ribosomal FUS interacting partners. (uky.edu)
• Production of the longer (PP1ab) or shorter protein (PP1a) depends on a -1 ribosomal frameshifting event. (micrornaprofile.com)

Motifs2

• A modified version of the IQ motif as a consensus for Ca2+-independent binding and two related motifs for Ca2+-dependent binding, termed 18-14 and 1-5-10 based on the position of conserved hydrophobic residues, are proposed. (embl.de)
• Although considerable sequence diversity is observed among the different binding regions, these three classes of recognition motifs exist for many of the known CaM binding proteins. (embl.de)

Pathways5

• A wide variety of interacting proteins were identified and they are involved in a multitude of pathways including: chromosomal organization, transcription, RNA splicing, RNA transport, localized translation, and stress response. (uky.edu)
• Further pathway and disease association analysis suggested that proteins associated with translation and RNA quality control pathways may be the most significant. (uky.edu)
• These data suggest that PKC may regulate interactions of EWS and other RNA-binding proteins with their RNA targets and that IQ domains may provide a regulatory link between Ca2+ signal transduction pathways and RNA processing. (embl.de)
• In addition, Ling and colleagues' paper describes one possible way TDP-43 and FUS pathways could intersect. (alzforum.org)
• A full understanding of neuronal PIWI-piRNA pathways will ultimately provide novel insights into small RNA biology and could potentially provide precise targets for therapeutic applications. (molcells.org)

Aggregate1

• The RNA sequence in the vaccine [3] contains sequences believed to induce TDP-43 and FUS to aggregate in their prion-based conformation leading to the development of common neurodegerative diseases. (eatingtoascend.com)

Amyotrophic3

• Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) share overlapping genetic causes and disease symptoms, and are linked neuropathologically by the RNA binding protein TDP-43 (TAR DNA binding protein-43 kDa). (nature.com)
• TDP-43 is intimately linked with amyotrophic lateral sclerosis, but the mystery remains as to what the protein is normally meant to do, and what goes wrong when it mutates. (alzforum.org)
• A wealth of knowledge has been published on a class of RNA binding proteins shown to participating in causing a number of neurological diseases including Alzheimer's disease and ALS (Amyotrophic Lateral Sclerosis). (eatingtoascend.com)

Molecules4

• For example, proteins that are normally unfolded or relatively unstable as monomers (that is, as single, unbound protein molecules) are more likely to misfold into an abnormal conformation. (wikipedia.org)
• G-quadruplexes are secondary semi-stable folded structures found in our DNA and RNA which tend to assemble around guanine-rich sequences in the presence of cation molecules like potassium. (anti-agingfirewalls.com)
• IVT reactions enable the cost-effective production of longer circular RNA molecules, making enzymatic synthesis the current mainstream method for circular RNA synthesis. (techadda2.com)
• Circular RNAs (circRNAs) are regulatory molecules that show diverse functions. (oist.jp)

Drosophila3

• FUS/TLS is a member of the FET protein family that also includes the EWS protein, the TATA-binding protein TBP-associated factor TAFII68/TAF15, and the Drosophila cabeza/SARF protein. (wikipedia.org)
• Silencing of the Drosophila hnRNPA3 ortholog was deleterious and potentiated human FUS toxicity in the retina of transgenic flies. (worktribe.com)
• The PIWI protein was initially described in Drosophila , and its name, P-element-induced wimpy testis (PIWI), was assigned as a result of the destructive effect on testis development observed in PIWI knockout ( Lin and Spradling, 1997 ). (molcells.org)

Regulation1

• High-Resolution RNA Maps Suggest Common Principles of Splicing and Polyadenylation Regulation by TDP-43 , Cell Reports. (ulelab.info)

Genetic4

• The FUS protein also helps repair errors in DNA, which prevents cells from accumulating genetic damage. (medlineplus.gov)
• The genetic changes associated with these cancers are rearrangements (translocations) of genetic material between chromosome 16 (where the FUS gene is located) and other chromosomes. (medlineplus.gov)
• In an important model of premature aging, Werner's Syndrome, the genetic problem seems to be lack of a helicase protein that can unwind G-quadruplexes. (anti-agingfirewalls.com)
• Virus particles include the RNA genetic material and structural proteins needed for invasion of host cells. (micrornaprofile.com)

Gene expression1

• SARS-CoV-2 nonstructural proteins are responsible for viral transcription, replication, proteolytic processing, suppression of host immune responses and suppression of host gene expression. (micrornaprofile.com)

Pathogenesis1

• We concluded that mis-localization of these proteins potentially lead to their dysregulation or loss of function, thus contributing to FUS pathogenesis. (uky.edu)

Single-stranded2

• In simple terms, circular RNA is a closed single-stranded RNA molecule formed through covalent linkage at its ends. (techadda2.com)
• Description: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, positive-sense, single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). (micrornaprofile.com)

Sequences1

• The results indicate that the vaccine RNA has specific sequences that may induce TDP-43 and FUS to fold into their pathologic prion confirmations. (shtfplan.com)

Liposarcoma2

• Se han encontrado estas proteínas de fusión en el liposarcoma mixoide (LIPOSARCOMA MIXOIDE) y en la leucemia mieloide aguda. (bvsalud.org)
• These fusion proteins have been found in myxoid liposarcoma (LIPOSARCOMA, MYXOID) and acute myeloid leukemia. (bvsalud.org)

FTLD2

• A postzygotic de novo NCDN mutation identified in a sporadic FTLD patient results in neurochondrin haploinsufficiency and altered FUS granule dynamics. (ulaval.ca)
• Our study identifies the NCDN protein as a likely contributor of FTLD-FET pathophysiology. (ulaval.ca)

Interactions3

• His recent collaboration with Dr. Martha Hawes has led to the discovery that extracellular DNA, secreted DNases, and proteins are important immunity and pathogenicity factors in the plant-microbe interactions in the rhizosphere. (bio5.org)
• Two recent papers address these questions, focusing on TDP-43's stability and protein-protein interactions. (alzforum.org)
• We found that proteins within mFAs form significantly more physical interactions than those in SGs however mFAs fail to recruit many factors involved in signal transduction. (worktribe.com)

Species3

• The majority of proteins function as monodispersed ordered species dissolved in intra- or extra-cellular aqueous fluids. (frontiersin.org)
• Dr. Xiong is a 2012 winner of the Bill Gates and Melinda Foundation Grand Challenges Explorations in Global Health, and has more than 20 years of research experience on RNA viruses of important crops and native plant species. (bio5.org)
• PIWI Argonaute proteins and Piwi-interacting RNAs (piRNAs) are expressed in all animal species and play a critical role in cellular defense by inhibiting the activation of transposable elements in the germline. (molcells.org)

Toxicity2

• Furthermore, hUPF1, a human homologue of ECM32, also rescues the toxicity of FUS/TLS in this model, validating the yeast model and implicating a possible insufficiency in RNA processing or the RNA quality control machinery in the mechanism of FUS/TLS mediated toxicity. (cornell.edu)
• Examination of the effect of FUS/TLS expression on the decay of selected mRNAs in yeast indicates that the nonsense-mediated decay pathway is probably not the major determinant of either toxicity or suppression. (cornell.edu)

Synthesis3

• Julie is also working on a technique using a bright fluorescent protein, Venus, to monitor protein synthesis in a cell. (gatescambridge.org)
• Currently, the chemical synthesis of circular RNA primarily relies on phosphoramidite chemistry and solid-phase synthesis, using naturally occurring nucleoside triphosphate derivatives as building blocks. (techadda2.com)
• However, the current chemical synthesis technology for circular RNA can only generate circular RNAs with lengths of fewer than 70-80 nucleotides (nt). (techadda2.com)

Regulatory2

• piRNA is the most diverse class of regulatory RNAs in general. (molcells.org)
• The enclosed finding as well as additional potential risks leads the author to believe that regulatory approval of the RNA based vaccines for SARS-CoV-2 was premature and that the vaccine may cause much more harm than benefit. (eatingtoascend.com)

Pathologic1

• The paper goes on to state that "The folding of TDP-43 and FUS into their pathologic prion confirmations is known to cause ALS, front temporal lobar degeneration, Alzheimer's disease, and other neurological degenerative diseases. (shtfplan.com)

Mitochondrial proteins1

• We present one use case with a corpus of ~34 million text documents downloaded online to provide an example of elucidating the role of mitochondrial proteins in distinct cardiovascular disease phenotypes using this method. (bvsalud.org)

Domains3

• 2023). Defining RNA oligonucleotides that reverse deleterious phase transitions of RNA-binding proteins with prion-like domains. (upenn.edu)
• There are 165951 IQ domains in 60575 proteins in SMART's nrdb database. (embl.de)
• A) Domains of the PIWI protein. (molcells.org)

Fusion proteins1

• CHOP) conferring a strong transcriptional activation domain onto the fusion proteins. (wikipedia.org)

Transcription4

• In these instances, the promoter and N-terminal part of FUS/TLS is translocated to the C-terminal domain of various DNA-binding transcription factors (e.g. (wikipedia.org)
• In addition recognition sites for the transcription factors AP2, GCF, Sp1 have been identified in FUS. (wikipedia.org)
• Beyond nucleic acid binding, FUS/TLS was also found to associate with both general and more specialized protein factors to influence the initiation of transcription. (wikipedia.org)
• Once inside the cell the infecting RNA is used to encode structural proteins that make up virus particles, nonstructural proteins that direct virus assembly, transcription, replication and host control and accessory proteins whose function has not been determined. (micrornaprofile.com)

Motif2

• Short calmodulin-binding motif containing conserved Ile and Gln residues. (embl.de)
• Calmodulin-binding motif. (embl.de)

20231

• 2023). Genome-wide RNA binding analysis of C9orf72 poly(PR) dipeptides. (upenn.edu)

HnRNPA12

• Most notably, FUS interacted with hnRNPA1 and Matrin-3, proteins also known to cause familial ALS. (uky.edu)
• These proteins include FUS, TDP-43 and hnRNPA1, A2 and A3. (uni-muenchen.de)

Kinase3

• Acts as a 'third messenger' substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. (embl.de)
• The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain. (embl.de)
• Here we report that EWS, a nuclear RNA-binding prooncoprotein, contains an IQ domain, is phosphorylated by protein kinase C, and interacts with calmodulin. (embl.de)

Antibody2

• Micrograph of a section of the cerebral cortex from a person with Alzheimer's disease , immunostained with an antibody to amyloid beta (brown), a protein fragment that accumulates in amyloid plaques and cerebral amyloid angiopathy . (wikipedia.org)
• Human IgG antibody Laboratories manufactures the pan sars rna test reagents distributed by Genprice. (micrornaprofile.com)

Interacts1

• Indeed, FUS/TLS interacts with several nuclear receptors. (wikipedia.org)

Prion disease2

• [20] They have been most thoroughly studied with regard to prion disease , and are referred to as protein strains . (wikipedia.org)
• The article, titled "COVID-19 RNA Based Vaccines and the Risk of Prion Disease," was published in January of 2021 and has been studiously ignored by the mainstream media, which has focused its efforts on encouraging individuals to take the jab. (shtfplan.com)

Nucleus2

• The FUS gene provides instructions for making a protein that is found within the cell nucleus in most tissues and is involved in many of the steps of protein production. (medlineplus.gov)
• In our lab we are specifically interested in RNA binding proteins, which are cleared from the nucleus and deposited in the cytsosol. (uni-muenchen.de)

Neuronal1

• At week 24, those receiving tofersen showed a reduction in concentrations of toxic SOD1 protein and markers of neuronal injury. (cdc.gov)

Structures1

• T4 Dnl and T4 Rnl 1 are suitable for circularizing RNA without complex secondary structures, while T4 Rnl 2 is more appropriate for linear RNA precursors with double-stranded adapter regions. (techadda2.com)

Structural proteins1

• In addition to structural proteins (e.g. (bvsalud.org)

Phosphorylation1

• Interestingly, PKC phosphorylation of EWS inhibits its binding to RNA homopolymers, and conversely, RNA binding to EWS interferes with PKC phosphorylation. (embl.de)

Molecular2

• Here, we analysed two deep mutational scanning experiments to investigate the role of protein aggregation in molecular evolution. (frontiersin.org)
• Here, we set to clarify this complex matter and question of whether aggregation is an important constraint in protein evolution that can be the discriminant between beneficial and detrimental situations by considering two cases: we studied molecular evolution of proteins in an endogenous vs. exogenous host. (frontiersin.org)