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Norway

PMID:29799838  

Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development.

Seth D Kasowitz | Jun Ma | Stephen J Anderson | N Adrian Leu | Yang Xu | Brian D Gregory | Richard M Schultz | P Jeremy Wang
PLoS genetics | 2018

The N6-methyladenosine (m6A) modification is the most prevalent internal RNA modification in eukaryotes. The majority of m6A sites are found in the last exon and 3' UTRs. Here we show that the nuclear m6A reader YTHDC1 is essential for embryo viability and germline development in mouse. Specifically, YTHDC1 is required for spermatogonial development in males and for oocyte growth and maturation in females; Ythdc1-deficient oocytes are blocked at the primary follicle stage. Strikingly, loss of YTHDC1 leads to extensive alternative polyadenylation in oocytes, altering 3' UTR length. Furthermore, YTHDC1 deficiency causes massive alternative splicing defects in oocytes. The majority of splicing defects in mutant oocytes are rescued by introducing wild-type, but not m6A-binding-deficient, YTHDC1. YTHDC1 is associated with the pre-mRNA 3' end processing factors CPSF6, SRSF3, and SRSF7. Thus, YTHDC1 plays a critical role in processing of pre-mRNA transcripts in the oocyte nucleus and may have similar non-redundant roles throughout fetal development.

Pubmed ID: 29799838

Associated grants

  • Agency: NICHD NIH HHS, United States
    Id: R01 HD022681
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM118052
  • Agency: NIH HHS, United States
    Id: R01HD022681

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