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U1 snRNP increases RNA Pol II elongation rate to enable synthesis of long genes

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE218135 | GEO | 2023/03/24

REPOSITORIES: GEO

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U1 snRNP increases RNA Pol II elongation rate to enable synthesis of long genes [TT-Seq]

Project description:The expansion of introns within mammalian genomes poses a challenge for the production of full-length messenger RNAs (mRNA)s, with increasing evidence that these long AT-rich sequences present obstacles to transcription. Here, we investigate RNAPII elongation in mammalian cells at high resolution and demonstrate that RNAPII transcribes faster across introns. Moreover, we find that this acceleration is mediated by the association of U1 snRNP (U1) with the elongation complex at 5’ splice sites. The direct stimulation of elongation rate through introns by U1 reduces the occurrence of both premature termination and transcriptional arrest, thereby dramatically increasing RNA production. We further show that changes in RNAPII elongation rate due to AT-content and U1 binding explain previous reports of pausing or termination at splice junctions and the edge of CpG islands. We propose that this role for U1 has evolved to mitigate the risks that long, AT-rich intronic sequences pose to transcript completion.

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U1 snRNP increases RNA Pol II elongation rate to enable synthesis of long genes [PRO-seq]

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U1 snRNP increases RNA Pol II elongation rate to enable synthesis of long genes [PAC-seq]

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