PI3K/AKT signaling determines a dynamic switch between distinct KSRP functions favoring skeletal myogenesis.

Roberto Gherzi (1) , Paola Briata (1) , Wei-Jye Lin (1) , Matteo Giovarelli (1) , Michela Pasero (1) , Chu-Fang Chou (1) , Ching-Yi Chen (1) , Michele Trabucchi (1) , Michael Rosenfeld (1)

1 Experimental Oncology

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.

Mots clés: myogenesis; mRNA degradation; microRNA maturation; RNA-binding protein

Domaines: Biologie cellulaire

Roberto Gherzi, Paola Briata, Wei-Jye Lin, Matteo Giovarelli, Michela Pasero, et al.. PI3K/AKT signaling determines a dynamic switch between distinct KSRP functions favoring skeletal myogenesis.. Cell Death and Differentiation, 2011, ⟨10.1038/cdd.2011.117⟩. ⟨hal-00675790⟩