spermatocyte Proteomic. Mus musculus

METTL16 is reported recently to catalyze the formation of N6-methyl-adenosine (m6A) which involves in regulating several biological processes. However, the role of Mettl16 in male germ cells remains elusive. Herein, we identify the essential functions for METTL16 in meiotic prophase I using an inducible germline-specific inactivation strategy. METTL16 deficiency causes failed DDR proteins expansion to chromatin-wide region among sex chromosomes, inter-sister chromatids abnormal synapsis, and delayed DSB formation. Depletion of METTL16 results in an enormous deregulation of transcriptome in pachytene spermatocytes, and 80% of differential genes on sex chromosomes undergo upregulation. METTL16 cooperates with FUS/EWSR1 to regulate DSB formation in early meiotic prophase I, and also interacts with H2AX/MDC1/SCML2/MacroH2A1 which are closely related to MSCI. Furthermore, METTL16 interacts with translational initiation factor eIF3B in spermatocytes. Using MeRIP-seq, we found decreased m6A level in RNAs of some genes related to meiosis process like Ankrd31, Mdc1, Smc3, Rpa2 etc. Our results demonstrate that the involvement of METTL16 in meiosis progression is through cooperating with translational complex and modulating m6A modification on some specific genes, which creatively reveal the indispensable roles of methyltransferase METTL16 in meiosis progression.