NCBI Summary:
This gene encodes a member of the YTH (YT521-B homology) superfamily containing YTH domain. The YTH domain is typical for the eukaryotes and is particularly abundant in plants. The YTH domain is usually located in the middle of the protein sequence and may function in binding to RNA. In addition to a YTH domain, this protein has a proline rich region which may be involved in signal transduction. An Alu-rich domain has been identified in one of the introns of this gene, which is thought to be associated with human longevity. In addition, reciprocal translocations between this gene and the Runx1 (AML1) gene on chromosome 21 has been observed in patients with acute myeloid leukemia. This gene was initially mapped to chromosome 14, which was later turned out to be a pseudogene. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Oct 2012]
General function
RNA metabolism, RNA processing
Comment
Cellular localization
Comment
Ovarian function
Oocyte maturation, Early embryo development
Comment
m(6)A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition. Zhao BS et al. (2017) The maternal-to-zygotic transition (MZT) is one of the most profound and tightly orchestrated processes during the early life of embryos, yet factors that shape the temporal pattern of vertebrate MZT are largely unknown. Here we show that over one-third of zebrafish maternal messenger RNAs (mRNAs) can be N(6)-methyladenosine (m(6)A) modified, and the clearance of these maternal mRNAs is facilitated by an m(6)A-binding protein, Ythdf2. Removal of Ythdf2 in zebrafish embryos decelerates the decay of m(6)A-modified maternal mRNAs and impedes zygotic genome activation. These embryos fail to initiate timely MZT, undergo cell-cycle pause, and remain developmentally delayed throughout larval life. Our study reveals m(6)A-dependent RNA decay as a previously unidentified maternally driven mechanism that regulates maternal mRNA clearance during zebrafish MZT, highlighting the critical role of m(6)A mRNA methylation in transcriptome switching and animal development.//////////////////
Expression regulated by
Comment
Ovarian localization
Oocyte
Comment
Follicle stages
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: type: null mutation fertility: infertile - ovarian defect Comment: The RNA m(6)A Reader YTHDF2 Is Essential for the Post-transcriptional Regulation of the Maternal Transcriptome and Oocyte Competence. Ivanova I et al. (2017) YTHDF2 binds and destabilizes N(6)-methyladenosine (m(6)A)-modified mRNA. The extent to which this branch of m(6)A RNA-regulatory pathway functions in vivo and contributes to mammalian development remains unknown. Here we find that YTHDF2 deficiency is partially permissive in mice and results in female-specific infertility. Using conditional mutagenesis, we demonstrate that YTHDF2 is autonomously required within the germline to produce MII oocytes that are competent to sustain early zygotic development. Oocyte maturation is associated with a wave of maternal RNA degradation, and the resulting relative changes to the MII transcriptome are integral to oocyte quality. The loss of YTHDF2 results in the failure to regulate transcript dosage of a cohort of genes during oocyte maturation, with enrichment observed for the YTHDF2-binding consensus and evidence of m(6)A in these upregulated genes. In summary, the m(6)A-reader YTHDF2 is an intrinsic determinant of mammalian oocyte competence and early zygotic development.//////////////////