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

Sara Luzzi, Ugo Szachnowski, Sarah Greener, Kenny Schumacher, Stuart Fulton, Camille Gautier, Kang Hoo Han, Jack Darke, Rossana Piccinno, Anne Lafon, B. Franklin Pugh, Didier Devys, View ORCID ProfileLaszlo Tora, Antonin Morillon, Manolis Papamichos-Chronakis
doi: https://doi.org/10.1101/2020.03.02.973685
Sara Luzzi
1Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom
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Ugo Szachnowski
2ncRNA, Epigenetic, and Genome Fluidity, Institut Curie, PSL Research University, CNRS UMR 3244, Pierre et Marie Curie University, 26 rue d’Ulm, 75248 Paris Cedex 05, France
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Sarah Greener
1Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom
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Kenny Schumacher
3Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404, Illkirch, France
4Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France
5Institut National de la Santé et de la Recherche Médicale, U964, 67404, Illkirch, France
6Université de Strasbourg, 67404, Illkirch, France
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Stuart Fulton
7Department of Molecular Physiology and Cell Signaling, Institute of Systems, Molecular, and Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK
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Camille Gautier
2ncRNA, Epigenetic, and Genome Fluidity, Institut Curie, PSL Research University, CNRS UMR 3244, Pierre et Marie Curie University, 26 rue d’Ulm, 75248 Paris Cedex 05, France
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Kang Hoo Han
8Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA
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Jack Darke
1Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom
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Rossana Piccinno
9Institut Curie, PSL Research University, CNRS, UMR3664, 26 rue d’Ulm, 75248 Paris, France
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Anne Lafon
2ncRNA, Epigenetic, and Genome Fluidity, Institut Curie, PSL Research University, CNRS UMR 3244, Pierre et Marie Curie University, 26 rue d’Ulm, 75248 Paris Cedex 05, France
9Institut Curie, PSL Research University, CNRS, UMR3664, 26 rue d’Ulm, 75248 Paris, France
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B. Franklin Pugh
8Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA
10Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
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Didier Devys
3Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404, Illkirch, France
4Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France
5Institut National de la Santé et de la Recherche Médicale, U964, 67404, Illkirch, France
6Université de Strasbourg, 67404, Illkirch, France
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Laszlo Tora
3Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404, Illkirch, France
4Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France
5Institut National de la Santé et de la Recherche Médicale, U964, 67404, Illkirch, France
6Université de Strasbourg, 67404, Illkirch, France
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  • ORCID record for Laszlo Tora
Antonin Morillon
2ncRNA, Epigenetic, and Genome Fluidity, Institut Curie, PSL Research University, CNRS UMR 3244, Pierre et Marie Curie University, 26 rue d’Ulm, 75248 Paris Cedex 05, France
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  • For correspondence: antonin.morillon@curie.fr manolis.papamichos@newcastle.ac.uk
Manolis Papamichos-Chronakis
4Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France
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  • For correspondence: antonin.morillon@curie.fr manolis.papamichos@newcastle.ac.uk
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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.

Competing Interest Statement

The authors have declared no competing interest.

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Chromatin remodelling by INO80 at promoter proximal pause sites promotes premature termination of mRNA synthesis
Sara Luzzi, Ugo Szachnowski, Sarah Greener, Kenny Schumacher, Stuart Fulton, Camille Gautier, Kang Hoo Han, Jack Darke, Rossana Piccinno, Anne Lafon, B. Franklin Pugh, Didier Devys, Laszlo Tora, Antonin Morillon, Manolis Papamichos-Chronakis
bioRxiv 2020.03.02.973685; doi: https://doi.org/10.1101/2020.03.02.973685
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Chromatin remodelling by INO80 at promoter proximal pause sites promotes premature termination of mRNA synthesis
Sara Luzzi, Ugo Szachnowski, Sarah Greener, Kenny Schumacher, Stuart Fulton, Camille Gautier, Kang Hoo Han, Jack Darke, Rossana Piccinno, Anne Lafon, B. Franklin Pugh, Didier Devys, Laszlo Tora, Antonin Morillon, Manolis Papamichos-Chronakis
bioRxiv 2020.03.02.973685; doi: https://doi.org/10.1101/2020.03.02.973685

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