期刊
MOLECULAR CELL
卷 68, 期 2, 页码 374-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2017.09.021
关键词
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资金
- Boehringer Ingelheim Fonds PhD Fellowship
- Swiss National Science Foundation: ERC Transfer Grant (GermMethylation)
- project grant (Origin-of-pi)
- NCCR RNA and Disease Network
- Agence National de la Recherche (GuidedMethylation) [ANR-14-CE10-0011-02]
- Republic and Canton of Geneva
- Agence Nationale de la Recherche (ANR) [ANR-14-CE10-0011] Funding Source: Agence Nationale de la Recherche (ANR)
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.
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