E-GEOD-57113 - Destabilization of Nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fiber formation

Status
Released on 26 April 2014, last updated on 3 June 2014
Organism
Mus musculus
Samples (4)
Array (1)
Protocols (7)
Description
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
Experiment type
transcription profiling by array 
Contacts
Imed Gallouzi <imed.gallouzi@mcgill.ca>, Anne Cammas, Brenda J Sanchez, Carol Wilusz, Imed-Eddine Gallouzi, Isabel Lopez de Silanes, Jennifer F Ma, John Richardson, Kate van der Giessen, Matteo Giovarelli, Myriam Gorospe, Roberto Gherzi, Sergio Di Marco, Stefania Millevoi, Virginie Dormoy-Raclet, Xian J Lian
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-57113.idf.txt
Sample and data relationshipE-GEOD-57113.sdrf.txt
Processed data (1)E-GEOD-57113.processed.1.zip
Array designA-GEOD-17567.adf.txt
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