TY - JOUR
T1 - Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation
AU - Cammas, Anne
AU - Sanchez, Brenda Janice
AU - Lian, Xian Jin
AU - Dormoy-Raclet, Virginie
AU - Van Der Giessen, Kate
AU - De Silanes, Isabel López
AU - Ma, Jennifer
AU - Wilusz, Carol
AU - Richardson, John
AU - Gorospe, Myriam
AU - Millevoi, Stefania
AU - Giovarelli, Matteo
AU - Gherzi, Roberto
AU - Di Marco, Sergio
AU - Gallouzi, Imed Eddine
PY - 2014/6/27
Y1 - 2014/6/27
N2 - HuR promotes myogenesis by stabilizing the MyoD, myogenin and p21 mRNAs during the fusion of muscle cells to form myotubes. Here we show that HuR, via a novel mRNA destabilizing activity, promotes the early steps of myogenesis by reducing the expression of the cell cycle promoter nucleophosmin (NPM). Depletion of HuR stabilizes the NPM mRNA, increases NPM protein levels and inhibits myogenesis, while its overexpression elicits the opposite effects. NPM mRNA destabilization involves the association of HuR with the decay factor KSRP as well as the ribonuclease PARN and the exosome. The C terminus of HuR mediates the formation of the HuR-KSRP complex and is sufficient for maintaining a low level of the NPM mRNA as well as promoting the commitment of muscle cells to myogenesis. We therefore propose a model whereby the downregulation of the NPM mRNA, mediated by HuR, KSRP and its associated ribonucleases, is required for proper myogenesis.
AB - HuR promotes myogenesis by stabilizing the MyoD, myogenin and p21 mRNAs during the fusion of muscle cells to form myotubes. Here we show that HuR, via a novel mRNA destabilizing activity, promotes the early steps of myogenesis by reducing the expression of the cell cycle promoter nucleophosmin (NPM). Depletion of HuR stabilizes the NPM mRNA, increases NPM protein levels and inhibits myogenesis, while its overexpression elicits the opposite effects. NPM mRNA destabilization involves the association of HuR with the decay factor KSRP as well as the ribonuclease PARN and the exosome. The C terminus of HuR mediates the formation of the HuR-KSRP complex and is sufficient for maintaining a low level of the NPM mRNA as well as promoting the commitment of muscle cells to myogenesis. We therefore propose a model whereby the downregulation of the NPM mRNA, mediated by HuR, KSRP and its associated ribonucleases, is required for proper myogenesis.
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U2 - 10.1038/ncomms5190
DO - 10.1038/ncomms5190
M3 - Article
C2 - 24969639
AN - SCOPUS:84903647947
VL - 5
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 4190
ER -