A Complex of U1 snRNP with Cleavage and Polyadenylation Factors Controls Telescripting, Regulating mRNA Transcription in Human Cells.
Mol Cell, 2019/11/21;76(4):590-599.e4.
So BR[1], Di C[1], Cai Z[1], Venters CC[1], Guo J[1], Oh JM[1], Arai C[1], Dreyfuss G[2]
Affiliations
PMID: 31522989DOI: 10.1016/j.molcel.2019.08.007
Impact factor: 19.328
Abstract
Full-length transcription in the majority of human genes depends on U1 snRNP (U1) to co-transcriptionally suppress transcription-terminating premature 3' end cleavage and polyadenylation (PCPA) from cryptic polyadenylation signals (PASs) in introns. However, the mechanism of this U1 activity, termed telescripting, is unknown. Here, we captured a complex, comprising U1 and CPA factors (U1-CPAFs), that binds intronic PASs and suppresses PCPA. U1-CPAFs are distinct from U1-spliceosomal complexes; they include CPA's three main subunits, CFIm, CPSF, and CstF; lack essential splicing factors; and associate with transcription elongation and mRNA export complexes. Telescripting requires U1:pre-mRNA base-pairing, which can be disrupted by U1 antisense oligonucleotide (U1 AMO), triggering PCPA. U1 AMO remodels U1-CPAFs, revealing changes, including recruitment of CPA-stimulating factors, that explain U1-CPAFs' switch from repressive to activated states. Our findings outline this U1 telescripting mechanism and demonstrate U1's unique role as central regulator of pre-mRNA processing and transcription.
Keywords: -end processing; U1 snRNP; cleavage and polyadenylation; mRNA 3ʹ; telescripting; transcription elongation; transcription termination
MeSH terms
3' Untranslated Regions; Active Transport, Cell Nucleus; Binding Sites; Cell Nucleus; Cleavage And Polyadenylation Specificity Factor; Cleavage Stimulation Factor; HeLa Cells; Humans; Multiprotein Complexes; Poly A; Protein Binding; RNA Cleavage; RNA Precursors; RNA, Messenger; Ribonucleoprotein, U1 Small Nuclear; Transcription, Genetic
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