snRNP

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

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.

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.

Abstract: Patients with systemic lupus erythematosus often possess antibodies against two nuclear antigens called Sm and RNP (ribonucleoprotein). We have established the molecular identity of these antigens by analyzing immune precipitates of nuclear extracts from mouse Ehrlich ascites cells labeled with 32P and 35S. Anti-Sm serum selectively precipitates six small nuclear RNA molecules (snRNAs); anti-RNP serum reacts with only two of these; and a third serum, characterized as mostly anti-RNP, precipitates a subset of three snRNA bands. Three of the six RNAs are identified by fingerprint analysis as the previously characterized and highly abundant nucleoplasmic snRNA species U1a (171 nucleotides), U1b, and U2 (196 nucleotides). The other three RNAs (U4, U5, and U6) likewise are uridine rich and contain modified nucleotides, but they are smaller, with lengths of about 145, 120, and 95 residues, respectively. Each of the six snRNAs is complexed with and apparently antigenic by virtue of association with specific proteins. All three sera precipitate an identical complement of seven different polypeptides ranging in molecular weight from 12,000 to 35,000; these proteins are abundant in nuclear extracts, but are neither histones nor the major polypeptides comprising the 30S heterogeneous nuclear RNP particles of mammalian nuclei. Our data argue that each of the six snRNAs exists in a separate small nuclear ribonucleoprotein (snRNP) complex with a total molecular weight of about 175,000. We find that human antisera also precipitate snRNAs from a wide range of vertebrate species and from arthropods. We discuss the antigenic snRNPs in relation to the published literature on snRNAs and nuclear RNPs and consider possible functions of snRNPs in nuclear processes.