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Destabilization of Nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fiber formation

ABSTRACT: HuR promotes myogenesis by stabilizing MyoD, Myogenin and p21 mRNAs during the fusion step 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 complex. 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 the HuR/KSRP complex and its associated ribonucleases, is required for proper myogenesis. RNA was extracted from C2C12 treated with siRNA against HuR and compared to control siRNA

ORGANISM(S): Mus musculus  

SUBMITTER: Xian J Lian  Matteo Giovarelli   Anne Cammas   Carol Wilusz   Sergio Di Marco   Isabel Lopez de Silanes   Imed-Eddine Gallouzi   Imed Gallouzi   Brenda J Sanchez   Roberto Gherzi   Stefania Millevoi   Myriam Gorospe   Kate van der Giessen   Jennifer F Ma   Virginie Dormoy-Raclet   John Richardson    

PROVIDER: E-GEOD-57113 | ArrayExpress | 2014-06-03



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