3'UTR shortening alleviates miRNA repression of mRNAs critical for muscle stem cell differentiation.

ABSTRACT: Alternative polyadenylation (APA) modulates gene expression by altering 3' untranslated region (3'UTR) length. Although 3'UTR lengthening typically accompanies cell differentiation, we unexpectedly observed preferential APA-mediated 3'UTR shortening events during muscle stem cell (satellite cell, SC) differentiation, coinciding with increased muscle-specific miRNAs (myomiRs) targeting at alternative 3'UTRs. Mechanistically, this shortening primarily results from reduced cleavage factor I (CFI) expression and allows transcripts to escape repression by differentiation-induced myomiRs. Interestingly, perturbation of mRNA 3'UTR shortening of multiple genes impairs myogenic differentiation. Focusing on Matr3-a gene linked to muscle disorders-we demonstrate that its APA-miRNA regulatory balance

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC12864877 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature