N6-methyladenosine (m6A) is an essential internal RNA modification that is critical for  gene expression control in most organisms. Proteins with a YTH domain recognize  m6A marks and are mediators of molecular functions like RNA splicing, mRNA decay  and translation control. Here we demonstrate that YTH domain-containing 2 (YTHDC2)  is an m6A reader that is essential for male and female fertility in mice. In mutant males,  mitotic spermatogonia fail to differentiate into meiotic spermatocytes. Analysis identifies  transcripts upregulated in the Yhtdc2 mutant testes to be those that are expressed in  purified spermatogonia, while high-throughput mapping of the m6A transcriptome in  the mouse male germline demonstrates the upregulated transcripts to be those that  are enriched in m6A marks. Our biochemical studies indicate that YTHDC2 is an RNAinduced  ATPase that fuels its 35 RNA helicase activity. Interestingly, we find an  RNA-independent interaction between the 53 exoribonuclease XRN1 and the  Ankyrin repeat of YTHDC2 that is wedged in between the two RecA helicase domains.  Our studies reveal a role for YTHDC2 in modulating the levels of m6A-modified  germline transcripts that is essential for successful meiosis. SOURCE: Ramesh Pillai (ramesh.pillai@unige.ch) -  University of Geneva

Pluto Bioinformatics

GSE102346: Regulation of m6A transcripts by the 35 RNA helicase YTHDC2 is essential for a successful meiotic program in the mammalian germline