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Nat Struct Mol Biol. 2016 Jul;23(7):663-72. doi: 10.1038/nsmb.3243. Epub 2016 Jun 6.

The transcription factor ERG recruits CCR4-NOT to control mRNA decay and mitotic progression.

Author information

1
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium.
2
GIGA-Molecular Biology in Diseases, ULg, Liège, Belgium.
3
BiGRe, Université Libre de Bruxelles (ULB), Bruxelles, Belgium.
4
Computer Science Department, ULB, Bruxelles, Belgium.
5
GIGA-Inflammation, Infection &Immunity, ULg, Liège, Belgium.
6
Faculté des Sciences, ULB, Gosselies, Belgium.
7
Department of Cellular and Molecular Medicine, University of Leuven (KUL), Leuven, Belgium.
8
Howard Hughes Medical Institute, Rockefeller University, New York, New York, USA.
9
GIGA-Cancer, ULg, Liège, Belgium.
10
Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA.
11
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

Control of mRNA levels, a fundamental aspect in the regulation of gene expression, is achieved through a balance between mRNA synthesis and decay. E26-related gene (Erg) proteins are canonical transcription factors whose previously described functions are confined to the control of mRNA synthesis. Here, we report that ERG also regulates gene expression by affecting mRNA stability and identify the molecular mechanisms underlying this function in human cells. ERG is recruited to mRNAs via interaction with the RNA-binding protein RBPMS, and it promotes mRNA decay by binding CNOT2, a component of the CCR4-NOT deadenylation complex. Transcriptome-wide mRNA stability analysis revealed that ERG controls the degradation of a subset of mRNAs highly connected to Aurora signaling, whose decay during S phase is necessary for mitotic progression. Our data indicate that control of gene expression by mammalian transcription factors may follow a more complex scheme than previously anticipated, integrating mRNA synthesis and degradation.

PMID:
27273514
DOI:
10.1038/nsmb.3243
[Indexed for MEDLINE]
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