UniProt ID: E7F1H9 |
FUNCTION: Specifically recognizes and binds N6-methyladenosine (m6A)- containing RNAs, and regulates their stability (PubMed:28192787). M6A is a modification present at internal sites of mRNAs and some non- coding RNAs and plays a role in mRNA stability and processing (By similarity). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs (By similarity). The YTHDF paralogs (ythdf1, ythdf2 and ythdf3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (By similarity). Plays a key role in maternal-to-zygotic transition during early embryonic development, the process during which maternally inherited mRNAs are degraded: acts by binding m6A-containing maternal mRNAs and promoting their degradation (PubMed:28192787). More than one- third of maternal mRNAs can be modified by m6A (PubMed:28192787). Binding to m6A-containing mRNAs results in mRNA degradation (By similarity). Also involved in hematopoietic stem cells specification by binding to m6A-containing mRNAs, such as notch1a, and promote their degradation (PubMed:28869969). The decreased Notch signaling following notch1a degradation promotes endothelial to hematopoietic transition (PubMed:28869969). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (By similarity). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (By similarity). {ECO:0000250|UniProtKB:Q9Y5A9, ECO:0000269|PubMed:28192787, ECO:0000269|PubMed:28869969}. SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9Y5A9}. Cytoplasm, P-body {ECO:0000250|UniProtKB:Q9Y5A9}. Cytoplasm, Stress granule {ECO:0000250|UniProtKB:Q9Y5A9}. Nucleus {ECO:0000250|UniProtKB:Q9Y5A9}. Note=Localizes to the cytosol and relocates to the nucleus following heat shock stress. Can partition into different structures: into P- bodies in unstressed cells, and into stress granules during stress. {ECO:0000250|UniProtKB:Q9Y5A9}. DEVELOPMENTAL STAGE: Ubiquitously expressed throughout early embryogenesis. {ECO:0000269|PubMed:28192787}. DOMAIN: The disordered regions have the ability to interact with each other and to 'phase separate' into liquid droplets within the cytosol following binding to mRNAs containing multiple m6A-modified residues. This leads to the partition of m6A-containing mRNAs into membraneless compartments, where mRNAs may be stored, degraded or used to transport mRNAs to dendritic arbors in neurons. {ECO:0000250|UniProtKB:Q9Y5A9}. DISRUPTION PHENOTYPE: Homozygous mutants from the first generation do not show any visible phenotype. Crossing homozygotes mutants together leads to lethality in around 70% of their progeny, because embryos do not developed past the one-cell stage. This lethality is probably mediated by defective sperm males. Defects are due to impaired decay of N6-methyladenosine (m6A)-modified maternal mRNAs, leading to impede zygotic genome activation. Embryos fail to initiate timely maternal-to- zygotic, undergo cell-cycle pause and remain developmentally delayed. {ECO:0000269|PubMed:28192787}. SIMILARITY: Belongs to the YTHDF family. YTHDF2 subfamily. {ECO:0000305}. |
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