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U6 snRNP inhibits the premature cleavage and polyadenylation of pre-mRNAs (3'-Seq)

ABSTRACT: U6 snRNP inhibits the premature cleavage and polyadenylation of pre-mRNAs (3'-Seq)

PROVIDER: PRJNA1053390 | ENA |

REPOSITORIES: ENA

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U6 snRNP inhibits the premature cleavage and polyadenylation of pre-mRNAs

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U6 snRNP inhibits the premature cleavage and polyadenylation of pre-mRNAs (3'-Seq)

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U1 snRNP complex with cleavage and polyadenylation factors controls mRNA transcription termination

Project description: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 U1 telescripting mechanism and demonstrate U1’s unique role as central-regulator of pre-mRNA processing and transcription.

2019-07-31 | GSE135140 | GEO

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