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Chromatin remodelling by INO80 at promoter proximal pause sites promotes premature termination of mRNA synthesis

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Abstract

Abstract How co-transcriptional RNA quality control is regulated remains poorly understood. Here, we report that in S. cerevisiae premature transcription termination of mRNAs is regulated by the evolutionarily conserved ATP-dependent chromatin remodeling INO80 complex. Loss of INO80 leads to an increase in promoter-proximally paused RNA Polymerase II and defective progression into the gene body. We show that promoter-proximal transcriptional pausing correlates with loading of RNA surveillance and transcription termination factors to mRNA transcripts. Cells lacking INO80 are defective for the Nrd1-Nab3-Sen1 (NNS)-dependent pathway for transcription termination at snRNA genes and promoter-proximally sites of mRNA genes. We demonstrate that INO80 promotes the association of the RNA surveillance and termination factor Nab2 with short promoter-proximal mRNA transcripts. We provide evidence that co-transcriptional recruitment of Nab2 to chromatin is regulated by INO80, which enables the interaction of Nab2 with the histone variant H2A.Z. Our work suggests a chromatin mechanism for premature transcription termination at promoter-proximally pausing sites, linking RNA quality control to the transcriptional process.
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Dates and versions

hal-03430529 , version 1 (16-11-2021)

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Sara Luzzi, Ugo Szachnowski, Sarah Greener, Kenny Schumacher, Stuart Fulton, et al.. Chromatin remodelling by INO80 at promoter proximal pause sites promotes premature termination of mRNA synthesis. 2021. ⟨hal-03430529⟩
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