YTHDF2 governs muscle size through a targeted modulation of proteostasis.

ABSTRACT: The regulation of proteostasis is fundamental for maintenance of muscle mass and function. Activation of the TGF-β pathway drives wasting and premature aging by favoring the proteasomal degradation of structural muscle proteins. Yet, how this critical post-translational mechanism is kept in check to preserve muscle health remains unclear. Here, we reveal the molecular link between the post-transcriptional regulation of m⁶A-modified mRNA and the modulation of SMAD-dependent TGF-β signaling. We show that the m⁶A-binding protein YTHDF2 is essential to determining postnatal muscle size. Indeed, muscle-specific genetic deletion of YTHDF2 impairs skeletal muscle growth and abrogates the response to hypertrophic stimuli. We report that YTHDF2 controls the mRNA stability of t

SUBMITTER: Gilbert CJ 

PROVIDER: S-EPMC10928198 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature