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

P Briata1, W-J Lin, M Giovarelli

  • 1Gene Expression Regulation Laboratory, Istituto Nazionale per la Ricerca sul Cancro, Largo R .Benzi 10, Genoa, Italy. paola.briata@istge.it

Cell Death and Differentiation
|September 3, 2011
PubMed

Insights

The RNA binding protein KSRP is crucial for muscle development by regulating myogenic micro-RNAs (miRNAs) processing. PI3K/AKT signaling controls KSRP, impacting muscle gene expression and regeneration.

Area of Science:

  • Molecular Biology
  • Muscle Physiology
  • RNA Biology

Background:

  • Skeletal myogenesis involves complex signaling pathways like PI3K/AKT.
  • Myogenic micro-RNAs (miRNAs) play a significant role in muscle biology.
  • miRNA processing is a key regulatory step influenced by extracellular signals.

Purpose of the Study:

  • To investigate the role of the RNA binding protein KSRP in myogenic miRNA processing.
  • To determine how PI3K/AKT signaling regulates KSRP function in myoblasts and muscle regeneration.

Main Methods:

  • Analysis of KSRP function in C2C12 myoblasts.
  • Utilizing KSRP knock-out mice to study muscle regeneration.
  • Investigating the impact of PI3K/AKT activation on KSRP activities.

Main Results:

  • KSRP is essential for the proper processing of primary myogenic miRNAs upon PI3K/AKT activation.
  • PI3K/AKT signaling differentially regulates KSRP, inhibiting myogenin mRNA decay and promoting miRNA maturation.
  • This regulatory switch by KSRP contributes to activating the myogenic program.

Conclusions:

  • KSRP acts as a critical mediator between PI3K/AKT signaling and myogenic miRNA processing.
  • KSRP's dual function regulation is key to controlling muscle gene expression during myogenesis and regeneration.
  • Targeting KSRP or its regulatory pathways could offer therapeutic strategies for muscle disorders.

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