Insights Into MOV10 Function In Diverse RNA Regulation Pathways In Early Germ Cells

Spermatogenesis is a precisely orchestrated program that the development of germ cell commences from SPCs(spermatogonial progenitor cells),which goes through mitotic proliferation,meiotic division and post-meiotic differentiation to produce haploid spermatozoa.The proliferation and differentiation of SPCs is essential for maintaining continues spermatogenesis in lifetime,which involves in complicated RNA regulation.The RNA helicases MOV10(Moloney leukemia virus 10)and MOV10L1(Moloney leukemia virus 10 like-1)are two homologues.The meiosis was blocked at the stage of zygotene in Mov10l1ko and the spermatogenesis was blocked at the stage of round spermatid in Mov10l1cko induced by Ngn3-Cre.The function of MOV10 in mammalian germ cells still remains unclear.Here we report that MOV10 is enriched in spermatogonia.shRNA(Small hairpin RNA)-mediated knockdown of Mov10 led to a drastic impact on the fate of SPCs accompanied by global disturbance of RNA homeostasis.We carrry further study on MOV10 regarding its molecular function by employing HITS-CLIP(Crosslinking-immunprecipitation and high-throughput sequencing),MOV10 extensively binds to mRNAs,IncRNAs(long non-coding RNA),miRNA precursors.MOV10 binding intensity on mRNAs is enhanced on those with longer 3'UTRs(3'-untranslated regions).Target mRNAs are enriched in metabolie process according to the Gene Ontology analysis and mTOR(mammalian target of rapamycin)signaling pathway according to KEGG pathway analysis.MOV10 directly binds to mtor,Raptor and Rictor.The latter two work as the core factor in mTORC1 and mTORC2 respectively.Spermatogonia accumulation and meiosis arrest were observed in Raptorcko induced by Ngn3-Cre.Strikingly,MOV10 associates with an array of components involved in a RNA splicing/processing network,and serves as a regulator for alternative splicing and miRNA biogenesis.These data expand the landscape of molecular basis of MOV10 function.Our study reveals that MOV10 is a versatile RBP(RNA-binding protein)involved in a broader RNA regulatory network and the mechanism of regulating proliferation in early germ cells.