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Dissecting the effects of sequence on transcription attenuation by the Restrictor complex

ABSTRACT: Dissecting the effects of sequence on transcription attenuation by the Restrictor complex

PROVIDER: PRJNA1198906 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31736700_1.fastq.gz	Fastqsanger.gz
	SRR31736700_2.fastq.gz	Fastqsanger.gz
	SRR31736701_1.fastq.gz	Fastqsanger.gz
	SRR31736701_2.fastq.gz	Fastqsanger.gz
	SRR31736702_1.fastq.gz	Fastqsanger.gz

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Dissecting the effects of sequence on transcription attenuation by the Restrictor complex [INSERT-Seq]

Project description:The eukaryotic genome is actively transcribed by RNA Polymerase II (RNAPII) to produce both messenger RNAs (mRNAs) and a repertoire of non-coding RNAs (ncRNAs). For genome integrity, RNAPII elongation and termination is tightly regulated to enable the full-length synthesis of mRNAs and the rapid turnover of many ncRNAs. The Restrictor Complex has recently been implicated in attenuating the expression of many ncRNAs, however the mechanism by which Restrictor suppresses gene expression remains unclear. Here, we address central questions regarding the specificity of Restrictor-mediated transcription attenuation.

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Dissecting the effects of sequence on transcription attenuation by the Restrictor complex [PRO-Seq]

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Dissecting the effects of sequence on transcription attenuation by the Restrictor complex [RNA-Seq]

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Dissecting the effects of sequence on transcription attenuation by the Restrictor complex [TT-Seq]

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Dissecting the effects of sequence on transcription attenuation by the Restrictor complex [PRO-Seq]

Project description:Dissecting the effects of sequence on transcription attenuation by the Restrictor complex [PRO-Seq]

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Project description:Dissecting the effects of sequence on transcription attenuation by the Restrictor complex [RNA-Seq]

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Dissecting the effects of sequence on transcription attenuation by the Restrictor complex [INSERT-Seq]

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Dissecting the effects of sequence on transcription attenuation by the Restrictor complex

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-05-23 | GSE284382 | GEO

PP1/PNUTS phosphatase binds the restrictor complex and stimulates RNA pol II transcription termination

Project description:The restrictor, ZC3H4/WDR82, terminates antisense transcription from bidirectional promoters, but its mechanism is poorly understood. We report that ZC3H4/WDR82 immunoprecipitate with PP1 phosphatase and its nuclear targeting subunit, PNUTS, which binds to WDR82. AlphaFold predicts a complex of PP1/PNUTS with restrictor where both PNUTS and ZC3H4 contact WDR82. A substrate trap, PP1H66K-PNUTS, comprising inactive PP1 fused to the PNUTS C-terminus antagonizes restrictor mediated termination whereas PP1WT-PNUTS has less effect suggesting that phosphatase activity is required for termination. One PP1/PNUTS substrate implicated in termination by restrictor is pol II CTD Ser5-P. PP1H66K-PNUTS induces Ser5-P hyperphosphorylation at 5’ ends presumably by inhibiting dephosphorylation. NET-seq analysis suggests that CTD Ser5 dephosphorylation would promote termination by increasing pol II pausing. Both inhibition of termination and CTD hyperphosphorylation require the WDR82 binding domain of PP1H66K-PNUTS that mediates restrictor binding. In summary, the PP1/PNUTS phosphatase associated with restrictor via WDR82 promotes efficient transcription termination.

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