Excess PrP^C inhibits muscle cell differentiation via miRNA-enhanced liquid-liquid phase separation implicated in myopathy.

ABSTRACT: The cellular prion protein (PrP^C) is required for skeletal muscle function. Here, we report that a higher level of PrP^C accumulates in the cytoplasm of the skeletal muscle of six myopathy patients compared to controls. PrP^C inhibits skeletal muscle cell autophagy, and blocks myoblast differentiation. PrP^C selectively binds to a subset of miRNAs during myoblast differentiation, and the colocalization of PrP^C and miR-214-3p was observed in the skeletal muscle of six myopathy patients with excessive PrP^C. We demonstrate that PrP^C is overexpressed in skeletal muscle cells under pathological conditions, inhibits muscle cell differentiation by physically interacting with a subset of miRNAs, and selectively recruits thes

SUBMITTER: Tao J 

PROVIDER: S-EPMC10709375 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature