title: PI3K/AKT signaling determines a dynamic switch between distinct KSRP functions favoring skeletal myogenesis.
abstract: 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.
authors: Gene Expression Regulation Laboratory, Istituto Nazionale per la Ricerca sul Cancro, Largo R .Benzi 10, Genoa, Italy. paola.briata@istge.it
authors: P
authors: P
authors: Briata
authors: W-J
authors: WJ
authors: Lin
authors: M
authors: M
authors: Giovarelli
authors: M
authors: M
authors: Pasero
authors: C-F
authors: CF
authors: Chou
authors: M
authors: M
authors: Trabucchi
authors: M G
authors: MG
authors: Rosenfeld
authors: C-Y
authors: CY
authors: Chen
authors: R
authors: R
authors: Gherzi
mesh_terms: D000818:Animals; D002460:Cell Line; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000293:injuries / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000378:metabolism*; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: C507913:Khsrp protein, mouse; D035683:MicroRNAs; C503801:Myog protein, mouse; D018008:Myogenin; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt