Preliminary Study Of MOV10L1-mediated Regulation Of Meiosis And Spermiogenesis Through Translation Mechanism

Spermatogenesis is a complicated and delicate process,in which key steps include meiosis,spermiogenesis among others.Dysfunction in any of these steps may cause spermatogenic arrest,leading to male infertility?Many studies have revealed that Mov10l1 is required in Spermatogenesis.MOV10L1,a RNA helicase,is specifically expressed in the male germ cells,it has been reported that MOV10L1 interacts with PIWI proteins and is involved in the primary processing of pachytene piRNA.MOV10L1 is required for piRNA-mediated transposons silencing,playing an important role in maintaining genome integrity.Results indicated that MOV10L1 may regulate mRNA translation or mRNA levels to influence the process of spermatogenesis,however the definite mechanism of MOV10L1 in meiosis and spermiogenesis in the male germline is not understood,as well as whether the RNA helicase MOV10L1 can directly regulate the expression of important protein in spermatogenesis remains unclear.The process of mRNA translation depends on the accuracy of the coding sequence.At the same time,it is also regulated by the structures in themselves.The untranslated Regions(UTRs)in mRNA can form RNA secondary structures by Waston-Crick and nonclassical base pairing,which influences the combination of important proteins and the recruiting of ribosomal proteinin in the translation process.G-quadruplex(G4)is a kind of GC-rich RNA sequences,which can fold into special secondary structure.It is confirmed that the G4 structure in 5 'UTR can regulate the process of mRNA translation by inducing cis acting element to translation inhibition.RNA helicase can unwind Double-strands RNA with the presense of ATP,whereas MOV10L1 as a member of the family of helicase,its role in relieving G4 RNA secondary structure and the underlying mechanism are still unknown.To study the role of MO V10L 1 in meiosis and spermiogenesis in the male germ cells and its potential mechanism,we produced the conditional knockout mice of Mov10l1 mediating by Ngn3-cre gene in the male grem cells.We characterized the expression of Mov10l1 in mice at different ages and spermatogenic cells of different types,as well as its protein localization in the cell.By analyzing the phenotype of the mutant mice,we found that disruption of the Mov1011 gene cause spermatogenic arrest at the early stage of round spermatid,with increased apoptosis observed in spermatogenic cells.Ch:romosome spread assay suggests that lack of Mov10l1 has no effect on the process of meiosis.Further,through the transcriptomics and proteomics analysis,combined with translation study system in vitro,we proved that MOV10L1 can relieve the inhibitory effect of G4 secondary structure on translation levels,and increase its target protein levels,such as MIW1 This discovery provides new insights into the mechanism by which Mov10l1 defects lead to male sterility,and thus expands the piRNA-independent role of MO V10L1 in male gametogenesis,Provides a new theoretical basis for future clinical practice.