Journal
CELL DEATH AND DIFFERENTIATION
Volume 19, Issue 3, Pages 478-487Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2011.117
Keywords
myogenesis; mRNA degradation; microRNA maturation; RNA-binding protein
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Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC)
- Association for International Cancer research (AICR) [10-0527]
- Limonte 2 (Regione Liguria, RNA Technology)
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Skeletal myogenesis is orchestrated by distinct regulatory signaling pathways, including PI3K/AKT, that ultimately control muscle gene expression. Recently discovered myogenic micro-RNAs (miRNAs) are deeply implicated in muscle biology. Processing of miRNAs from their primary transcripts is emerging as a major step in the control of miRNA levels and might be well suited to be regulated by extracellular signals. Here we report that the RNA binding protein KSRP is required for the correct processing of primary myogenic miRNAs upon PI3K/AKT activation in myoblasts C2C12 and in the course of injury-induced muscle regeneration, as revealed by Ksrp knock-out mice analysis. PI3K/AKT activation regulates in opposite ways two distinct KSRP functions inhibiting its ability to promote decay of myogenin mRNA and activating its ability to favor maturation of myogenic miRNAs. This dynamic regulatory switch eventually contributes to the activation of the myogenic program. Cell Death and Differentiation (2012) 19, 478-487; doi: 10.1038/cdd.2011.117; published online 2 September 2011
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