The transcription factor ERG recruits CCR4-NOT to control mRNA decay and mitotic progression.
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.
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium.|GIGA-Molecular Biology in Diseases, ULg, Liège, Belgium.
Xavier
0000-0002-5147-2863
X
Rambout
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium.|GIGA-Molecular Biology in Diseases, ULg, Liège, Belgium.
Cécile
C
Detiffe
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium.|GIGA-Molecular Biology in Diseases, ULg, Liège, Belgium.
Jonathan
J
Bruyr
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium.|GIGA-Molecular Biology in Diseases, ULg, Liège, Belgium.
Emeline
E
Mariavelle
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium.|GIGA-Molecular Biology in Diseases, ULg, Liège, Belgium.
Majid
M
Cherkaoui
BiGRe, Université Libre de Bruxelles (ULB), Bruxelles, Belgium.|Computer Science Department, ULB, Bruxelles, Belgium.
Sylvain
S
Brohée
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium.|GIGA-Molecular Biology in Diseases, ULg, Liège, Belgium.
Pauline
P
Demoitié
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium.|GIGA-Inflammation, Infection &Immunity, ULg, Liège, Belgium.
Marielle
M
Lebrun
Faculté des Sciences, ULB, Gosselies, Belgium.
Romuald
R
Soin
Department of Cellular and Molecular Medicine, University of Leuven (KUL), Leuven, Belgium.
Bart
B
Lesage
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium.|GIGA-Molecular Biology in Diseases, ULg, Liège, Belgium.
Katia
K
Guedri
Department of Cellular and Molecular Medicine, University of Leuven (KUL), Leuven, Belgium.
Monique
M
Beullens
Department of Cellular and Molecular Medicine, University of Leuven (KUL), Leuven, Belgium.
Mathieu
M
Bollen
Howard Hughes Medical Institute, Rockefeller University, New York, New York, USA.
Thalia A
TA
Farazi
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium.|GIGA-Molecular Biology in Diseases, ULg, Liège, Belgium.
Richard
R
Kettmann
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium.|GIGA-Cancer, ULg, Liège, Belgium.
Ingrid
I
Struman
Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA.|Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
David E
DE
Hill
Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA.|Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Marc
M
Vidal
Faculté des Sciences, ULB, Gosselies, Belgium.
Véronique
V
Kruys
BiGRe, Université Libre de Bruxelles (ULB), Bruxelles, Belgium.
Nicolas
N
Simonis
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium.|GIGA-Molecular Biology in Diseases, ULg, Liège, Belgium.
Jean-Claude
JC
Twizere
Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège (ULg), Liège, Belgium.|GIGA-Molecular Biology in Diseases, ULg, Liège, Belgium.
Franck
F
Dequiedt
D064127:Aurora Kinases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000071230:Transcriptional Regulator ERG / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
C485365:CNOT2 protein, human; C072312:ERG protein, human; C078433:FLI1 protein, human; D051789:Proto-Oncogene Protein c-fli-1; C101827:RBPMS protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D000071230:Transcriptional Regulator ERG; D064127:Aurora Kinases