PPP6R3-mediated dephosphorylation regulates mRNA translation during spermatogonial differentiation.

ABSTRACT: Protein dephosphorylation mediated by phosphatases regulates spermatogenesis. However, which proteins are dephosphorylated and how they regulate spermatogenesis are largely unknown. Here, we show that germline-specific deletion of protein phosphatase 6 regulatory subunit 3 (PPP6R3), which determines substrate specificity of protein phosphatase 6 (PP6), causes abnormal spermatogonial differentiation and male infertility, accompanied by translation inhibition. PPP6R3 directly interacts with EIF3C and EIF4G1 in KIT⁺ spermatogonia. Decreased levels of non-phosphorylated EIF3C and EIF4G1 after PPP6R3 deletion attenuate their enrichment for mRNAs associated with spermatogonial differentiation, and increased phosphorylation levels promote their degradation. Specifically, the phosphoryl

SUBMITTER: Fang Q 

PROVIDER: S-EPMC12304272 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature