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

[en] 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.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Rambout, Xavier ; Université de Liège > GIGA-Research

Detiffe, Cecile

Bruyr, Jonathan

Mariavelle, Emeline ; Université de Liège - ULiège > Molecular Biology of Diseases-Gene Expression & Cancer

Cherkaoui, Majid

Brohee, Sylvain

Demoitie, Pauline

Lebrun, Marielle ; Université de Liège > Département des sciences de la vie > GIGA-R : Virologie et immunologie

Soin, Romuald

Lesage, Bart

More authors (12 more)

Language :

English

Title :

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

Publication date :

2016

Journal title :

Nature Structural and Molecular Biology

ISSN :

1545-9993

eISSN :

1545-9985

Publisher :

Nature Publishing Group

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://reflexions.ulg.ac.be/en/GeneExpression
http://reflexions.ulg.ac.be/en/Wireworms

Available on ORBi :

since 16 June 2016

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