First Author | Wojtas MN | Year | 2017 |
Journal | Mol Cell | Volume | 68 |
Issue | 2 | Pages | 374-387.e12 |
PubMed ID | 29033321 | Mgi Jnum | J:243742 |
Mgi Id | MGI:5911610 | Doi | 10.1016/j.molcel.2017.09.021 |
Citation | Wojtas MN, et al. (2017) Regulation of m(6)A Transcripts by the 3'-->5' RNA Helicase YTHDC2 Is Essential for a Successful Meiotic Program in the Mammalian Germline. Mol Cell 68(2):374-387.e12 |
abstractText | N(6)-methyladenosine (m(6)A) is an essential internal RNA modification that is critical for gene expression control in most organisms. Proteins with a YTH domain recognize m(6)A 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 m(6)A reader that is essential for male and female fertility in mice. High-throughput mapping of the m(6)A transcriptome and expression analysis in the Yhtdc2 mutant testes reveal an upregulation of m(6)A-enriched transcripts. Our biochemical studies indicate that YTHDC2 is an RNA-induced ATPase with a 3'-->5' RNA helicase activity. Furthermore, YTHDC2 recruits the 5'-->3' exoribonuclease XRN1 via Ankyrin repeats that are inserted in between the RecA modules of the RNA helicase domain. Our studies reveal a role for YTHDC2 in modulating the levels of m(6)A-modified germline transcripts to maintain a gene expression program that is conducive for progression through meiosis. |