m6A related protein Mettl16 and YTHDC1 regulate spermatogonial differentiation

Spermatogenesis is a unique and intricate process that supports the production of millions of sperm daily in the testis. This highly efficient process is regulated at multiple levels. N6-methyladenosine (m6A), the most common internal modification in eukaryotic mRNA, has been reported to play an important role in transcriptional regulation during spermatogenesis. METTL16 has recently been identified as an RNA methyltransferase responsible for deposition of m6A with a consensus sequence AC(m6)AGAGA that can be recognized by the m6A-binding protein YTHDC1. Here, we employed the conditional knockout mouse model and explored the function of the m6A related proteins METTL16 and YTHDC1 in spermatogenesis. Our results showed that the male Mettl16vasa-cre mice had significantly smaller testes compared to the wildtype, and progressive loss of germ cells after birth. The deletion of Mettl16 or YTHDC1 in type A1 spermatogonia resulted in arrest in the differentiation of spermatogonia. Our data demonstrate that the writer METTL16 and reader YTHDC1 play an important role in the differentiation of spermatogonia.