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The PAF1 complex promotes 3‘ processing of pervasive transcripts [PRO-Seq]

ABSTRACT: The PAF1 complex (PAF1C) functions in multiple transcriptional and co-transcriptional processes. Although many aspects of the requirement for PAF1 in coding gene transcription have been heavily studied, the function of PAF1C at sites of non-coding transcription is poorly understood. eRNAs and PROMPTs are pervasive transcripts transcribed by RNA Polymerase II and rapidly degraded after 3’ endonucleolytic cleavage by the Integrator complex (Integrator). Here we show that PAF1C depletion results in near universal 3’ end processing defects in pervasive transcripts, leading to transcription termination dysregulation. Mechanistically, PAF1C recruits Integrator to chromatin through direct interactions promoting timely cleavage and transcription termination of pervasive transcripts. We also show that PAF1C recruits Integrator to the promoters of coding genes, where PAF1C then dissociates from the Integrator complex upon entry into processive elongation. Our results demonstrate an unexpected function for PAF1C in limiting the length and accumulation of pervasive transcripts, while highlighting a general requirement for PAF1C in Integrator recruitment.

ORGANISM(S): Mus musculus

PROVIDER: GSE163501 | GEO | 2022/03/15

REPOSITORIES: GEO

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The PAF1 complex promotes 3‘ processing of pervasive transcripts [ChIP-seq]

Project description:The PAF1 complex (PAF1C) functions in multiple transcriptional and co-transcriptional processes. Although many aspects of the requirement for PAF1 in coding gene transcription have been heavily studied, the function of PAF1C at sites of non-coding transcription is poorly understood. eRNAs and PROMPTs are pervasive transcripts transcribed by RNA Polymerase II and rapidly degraded after 3’ endonucleolytic cleavage by the Integrator complex (Integrator). Here we show that PAF1C depletion results in near universal 3’ end processing defects in pervasive transcripts, leading to transcription termination dysregulation. Mechanistically, PAF1C recruits Integrator to chromatin through direct interactions promoting timely cleavage and transcription termination of pervasive transcripts. We also show that PAF1C recruits Integrator to the promoters of coding genes, where PAF1C then dissociates from the Integrator complex upon entry into processive elongation. Our results demonstrate an unexpected function for PAF1C in limiting the length and accumulation of pervasive transcripts, while highlighting a general requirement for PAF1C in Integrator recruitment.

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The PAF1 complex promotes 3‘ processing of pervasive transcripts

Project description:The PAF1 complex (PAF1C) functions in multiple transcriptional processes involving RNA Polymerase II (Pol II). eRNAs and PROMPTs are pervasive transcripts transcribed by Pol II and rapidly degraded by the nuclear exosome complex after 3’ endonucleolytic cleavage by the Integrator complex (Integrator). Here we show that PAF1C has an unexpected role in the termination of eRNAs and PROMPTs that are cleaved 1-3 kb downstream of the transcription start site. Mechanistically, PAF1C facilitates recruitment of Integrator to sites of pervasive transcript cleavage, promoting timely cleavage and transcription termination. We also show that PAF1C recruits Integrator to coding genes, where PAF1C then dissociates from Integrator upon entry into processive elongation. Our results demonstrate an unexpected function for PAF1C in limiting the length and accumulation of pervasive transcripts that result from nonproductive transcription

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