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snRNP

About: snRNP is a research topic. Over the lifetime, 2551 publications have been published within this topic receiving 166239 citations. The topic is also known as: snRNP & Ribonucleoproteins, Small Nuclear.


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Journal ArticleDOI
TL;DR: An unexpected role for U1 homeostasis (available U1 relative to transcription) in oncogenic and activated cell states is revealed, and U1 is suggested as a potential target for their modulation.
Abstract: Stimulated cells and cancer cells have widespread shortening of mRNA 3'-untranslated regions (3'UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in introns and last exons. U1 snRNP (U1), vertebrates' most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread premature transcription termination and mRNA shortening. Here we show that low U1 AMO doses increase cancer cells' migration and invasion in vitro by up to 500%, whereas U1 over-expression has the opposite effect. In addition to 3'UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected role for U1 homeostasis (available U1 relative to transcription) in oncogenic and activated cell states, and suggest U1 as a potential target for their modulation.

3,432 citations

Journal ArticleDOI
TL;DR: A new role for circRNAs in regulating gene expression in the nucleus is revealed, in which EIciRNAs enhance the expression of their parental genes in cis, and a regulatory strategy for transcriptional control via specific RNA-RNA interaction between U1 snRNA and EICIRNAs is highlighted.
Abstract: Noncoding RNAs (ncRNAs) have numerous roles in development and disease, and one of the prominent roles is to regulate gene expression A vast number of circular RNAs (circRNAs) have been identified, and some have been shown to function as microRNA sponges in animal cells Here, we report a class of circRNAs associated with RNA polymerase II in human cells In these circRNAs, exons are circularized with introns 'retained' between exons; we term them exon-intron circRNAs or EIciRNAs EIciRNAs predominantly localize in the nucleus, interact with U1 snRNP and promote transcription of their parental genes Our findings reveal a new role for circRNAs in regulating gene expression in the nucleus, in which EIciRNAs enhance the expression of their parental genes in cis, and highlight a regulatory strategy for transcriptional control via specific RNA-RNA interaction between U1 snRNA and EIciRNAs

2,077 citations

Posted ContentDOI
09 Aug 2019-bioRxiv
TL;DR: It is shown that U1 AMO also modulates cancer cells’ phenotype, dose-dependently increasing migration and invasion in vitro by up to 500%, whereas U1 over-expression has the opposite effect.
Abstract: Stimulated cells and cancer cells have widespread shortening of mRNA 3’-utranslated regions (3’UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in the last exon and in introns. U1 snRNA (U1), vertebrates’ most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread mRNA shortening. Here we show that U1 AMO also modulates cancer cells’ phenotype, dose-dependently increasing migration and invasion in vitro by up to 500%, whereas U1 over-expression has the opposite effect. In addition to 3’UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected link between U1 regulation and oncogenic and activated cell states, and suggest U1 as a potential target for their modulation.

1,660 citations

Journal ArticleDOI
TL;DR: The extensive interplay of RNA and proteins in aligning the pre-mRNA's reactive groups, and the presence of both RNA and protein at the core of the splicing machinery, suggest that the spliceosome is an RNP enzyme, but elucidation of the precise nature of its active site awaits the generation of a high-resolution structure of its RNP core.
Abstract: Pre-mRNA splicing is catalyzed by the spliceosome, a multimegadalton ribonucleoprotein (RNP) complex comprised of five snRNPs and numerous proteins. Intricate RNA-RNA and RNP networks, which serve to align the reactive groups of the pre-mRNA for catalysis, are formed and repeatedly rearranged during spliceosome assembly and catalysis. Both the conformation and composition of the spliceosome are highly dynamic, affording the splicing machinery its accuracy and flexibility, and these remarkable dynamics are largely conserved between yeast and metazoans. Because of its dynamic and complex nature, obtaining structural information about the spliceosome represents a major challenge. Electron microscopy has revealed the general morphology of several spliceosomal complexes and their snRNP subunits, and also the spatial arrangement of some of their components. X-ray and NMR studies have provided high resolution structure information about spliceosomal proteins alone or complexed with one or more binding partners. The extensive interplay of RNA and proteins in aligning the pre-mRNA's reactive groups, and the presence of both RNA and protein at the core of the splicing machinery, suggest that the spliceosome is an RNP enzyme. However, elucidation of the precise nature of the spliceosome's active site, awaits the generation of a high-resolution structure of its RNP core.

1,436 citations

Journal ArticleDOI
10 Jan 1980-Nature
TL;DR: Several lines of evidence are presented that suggest a direct involvement of snRNPs in the splicing of hnRNA molecules, including the observation that the nucleotide sequence at the 5′ end of U1 RNA exhibits extensive complementarity to those across splice junctions in hn RNA molecules.
Abstract: Discrete, stable small RNA molecules are found in the nuclei of cells1 from a wide variety of eukaryotic organisms2. Many of these small nuclear RNA (snRNA) species, which range in size from about 90 to 220 nucleotides, have been well-characterised biochemically3–6, and some sequenced7,8. However, their function has remained obscure. The most abundant snRNA species exist as a closely related set of RNA–protein complexes called small nuclear ribonucleoproteins (snRNPs)9. snRNPs are the antigens recognised by antibodies from some patients with lupus erythematosus (LE), an autoimmune rheumatic disease10,11. Anti-RNP antibodies from lupus sera selectively precipitate snRNP species containing Ula7 and Ulb9 RNAs from mouse Ehrlich ascites cell nuclei, whereas anti-Sm antibodies bind these snRNPs and four others containing U2 (ref. 8), U4, US and U6 (ref. 9) RNAs. Both antibody systems precipitate the same seven prominent nuclear proteins (molecular weight 12,000–32,000). All molecules of the snRNAs U1, U2, U4, U5 and U6 appear to exist in the form of antigenic snRNPs9. The particles sediment at about 10S and each probably contains a single snRNA molecule. Indirect immunofluorescence studies (refs 12, 13, and unpublished observations) using anti-RNP and anti-Sm sera confirm the nuclear (but non-nucleolar) location of the antigenic snRNPs. Here we present several lines of evidence that suggest a direct involvement of snRNPs in the splicing of hnRNA. Most intriguing is the observation that the nucleotide sequence at the 5′ end of U1 RNA exhibits extensive complementarity to those across splice junctions in hnRNA molecules.

1,058 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20241
202333
202293
202164
202045
201947