CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3′-end processing

Judith Pirngruber; Andrei Shchebet; Lisa Schreiber; Efrat Shema; Neri Minsky; Rob D. Chapman; Dirk Eick; Yael Aylon; Moshe Oren; Steven A. Johnsen

doi:10.1038/embor.2009.108

CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3′-end processing

Judith Pirngruber, Andrei Shchebet, Lisa Schreiber, Efrat Shema, Neri Minsky, Rob D. Chapman, Dirk Eick, Yael Aylon, Moshe Oren, Steven A. Johnsen

Gastroenterology and Hepatology

Research output: Contribution to journal › Article › peer-review

121 Scopus citations

Abstract

Post-translational histone modifications have essential roles in controlling nuclear processes; however, the specific mechanisms regulating these modifications and their combinatorial activities remain elusive. Cyclin-dependent kinase 9 (CDK9) regulates gene expression by phosphorylating transcriptional regulatory proteins, including the RNA polymerase II carboxy-terminal domain. Here, we show that CDK9 activity is essential for maintaining global and gene-associated levels of histone H2B monoubiquitination (H2Bub1). Furthermore, CDK9 activity and H2Bub1 help to maintain correct replication-dependent histone messenger RNA (mRNA) 3′-end processing. CDK9 knockdown consistently resulted in inefficient recognition of the correct mRNA 3′-end cleavage site and led to increased read-through of RNA polymerase II to an alternative downstream polyadenylation signal. Thus, CDK9 acts to integrate phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing.

Original language	English (US)
Pages (from-to)	894-900
Number of pages	7
Journal	EMBO Reports
Volume	10
Issue number	8
DOIs	https://doi.org/10.1038/embor.2009.108
State	Published - 2009

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics

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10.1038/embor.2009.108

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title = "CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3′-end processing",

abstract = "Post-translational histone modifications have essential roles in controlling nuclear processes; however, the specific mechanisms regulating these modifications and their combinatorial activities remain elusive. Cyclin-dependent kinase 9 (CDK9) regulates gene expression by phosphorylating transcriptional regulatory proteins, including the RNA polymerase II carboxy-terminal domain. Here, we show that CDK9 activity is essential for maintaining global and gene-associated levels of histone H2B monoubiquitination (H2Bub1). Furthermore, CDK9 activity and H2Bub1 help to maintain correct replication-dependent histone messenger RNA (mRNA) 3′-end processing. CDK9 knockdown consistently resulted in inefficient recognition of the correct mRNA 3′-end cleavage site and led to increased read-through of RNA polymerase II to an alternative downstream polyadenylation signal. Thus, CDK9 acts to integrate phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing.",

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AU - Shchebet, Andrei

AU - Schreiber, Lisa

AU - Shema, Efrat

AU - Minsky, Neri

AU - Chapman, Rob D.

AU - Eick, Dirk

AU - Aylon, Yael

AU - Oren, Moshe

AU - Johnsen, Steven A.

PY - 2009

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AB - Post-translational histone modifications have essential roles in controlling nuclear processes; however, the specific mechanisms regulating these modifications and their combinatorial activities remain elusive. Cyclin-dependent kinase 9 (CDK9) regulates gene expression by phosphorylating transcriptional regulatory proteins, including the RNA polymerase II carboxy-terminal domain. Here, we show that CDK9 activity is essential for maintaining global and gene-associated levels of histone H2B monoubiquitination (H2Bub1). Furthermore, CDK9 activity and H2Bub1 help to maintain correct replication-dependent histone messenger RNA (mRNA) 3′-end processing. CDK9 knockdown consistently resulted in inefficient recognition of the correct mRNA 3′-end cleavage site and led to increased read-through of RNA polymerase II to an alternative downstream polyadenylation signal. Thus, CDK9 acts to integrate phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing.

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CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3′-end processing

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