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Insights into the U1 small nuclear ribonucleoprotein complex superfamily

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The 164 bp U1 small nuclear (sn) RNA is one of the most abundant noncoding (nc) RNA in human cells, estimated to be in the region of 106 copies/cell. Although best known for its role in pre‐messenger RNA (mRNA) splicing events, research over the past 20 years has revealed diverse functions of this ncRNA in mammalian cell types. Excellent reviews exist detailing the role of U1 snRNA in pre‐mRNA splicing events. This review highlights what is currently known regarding the additional roles, snRNP composition, expression profiles, and the genomic organization of this ncRNA. WIREs RNA 2015, 6:79–92. doi: 10.1002/wrna.1257 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications RNA Processing > Splicing Mechanisms
Composite figure illustrating the heterogeneity of the U1 and vU1 snRNAs. The U1 small nuclear RNA (snRNA) is illustrated in black in the form of a clover‐leaf structure. Base changes, which have been documented for human variant (v)U1 snRNAs located on chromosome 1q12‐21, are illustrated in red. Insertion of additional bases is denoted by a blue triangle. Deleted regions, associated with some vU1 snRNAs are denoted in grey. m32,2,7Gppp represents the snRNA‐specific trimethyl cap structure. The positions of the U1‐specific proteins U1‐70K (blue), U1‐A (green), U1‐C (yellow), and Sm proteins (brown) are illustrated. U1‐C does not associate with the U1 snRNA directly but interacts specifically with U1‐70K and Sm‐D3. U1‐70k specifically interacts with stem loop I (SLI) of the U1 snRNA and makes additional contacts with U1‐C and Sm‐B/B′ and Sm‐D3.
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U1 small nuclear RNA (snRNA) participates in transcription initiation and pre‐mRNA splicing. U1 snRNA is recruited to the transcription initiation complex by Taf15, which associates with the pre‐initiation complex either through protein:protein interactions with the general transcription factors (GTFs) or through recognition of specific promoter elements. Taf15 forms two complexes with the U1 snRNA: the U1 snRNA alone or as part of a ribonucleoprotein complex (U1 snRNA/RNP). Following initiation, TFIIH phosphorylates the C‐terminal domain of the large subunit of Pol II (black wavy line) to promote productive elongation. U1 snRNA interacts with the TFIIH associated kinase complex and is thought to enhance the rate of transcription initiation/re‐initiation. U1 snRNP also associates with the transcribing polymerase during productive elongation, which is thought to position U1 snRNA in close proximity to the emerging pre‐RNA to enhance base‐pairing interactions with the 5′ splice sites (*). Together with splicing factors (SR and hnRNP proteins), U2 snRNA and the Spliceosome, U1 snRNP facilitates excision of the intronic sequences and splices together the exonic sequences to generate a translatable mRNA. Figure is labelled as in Figure above with the addition of U2: U2 snRNP; SR: serine‐arginine splicing factors; hnRNP: heterogeneous nuclear ribonucleoproteins.
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U1/vU1 small nuclear RNAs (snRNAs) participates in pA site selection and Pol II directionality at promoters. U1 snRNA binding sites (*) are located at exon/intron junctions and within intronic and UTR regions of pre‐mRNAs. In addition, poly A (pA) hexamers are also found within intronic regions and the UTRs. If U1 snRNP associates with the pre‐mRNA in the vicinity of a pA site, both cleavage and polyadenylation at the pA site can be inhibited. The U1‐specific protein, U1‐70K, contributes to this block in polyadenylation by interfering with the association of the poly A polymerase (PAP), which adds a poly adenosine tail to the end of the mRNA. Depending on where U1 snRNA binds, varying length mRNAs can be generated as a result of cleavage/polyadenylation at internal ‘cryptic’ pA sites or alternative pA sites within the 3′UTRs (terminal pA sites). vU1 snRNPs, denoted in light green, have also been shown to participate in polyadenylation control. Motif analysis of regions flanking the promoters of human genes has confirmed specific enrichment of pA sites upstream and U1 snRNA binding sites downstream of the transcription start sites. Consequently, transcripts generated in the antisense direction are cleaved and polyadenylated early during transcription due to the lack of U1 snRNA binding sites to recruit U1 snRNP to block polyadenylation. These short polyadenylated RNAs are rapidly degraded by the exosome complex. Productive elongation by Pol II is favored in the sense direction owning to the increased number of U1 snRNA binding sites which enable U1 snRNA to bind and block cleavage/polyadenylation at internal cryptic pA sites in favor of proper polyadenylation at the end. The DNA and RNA are depicted as black and red lines, respectively. Exons are denoted as blue (DNA) or red boxes (RNA). The start of transcription is illustrated by an arrow. Differential phosphorylation of the C‐terminal domain of the large subunit of Pol II (black wavy line) throughout the transcription cycle is noted by ‘P’. Cap: m7G trimethy cap structure.
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RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
RNA Processing > Splicing Mechanisms

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