| Post Translational Modifications | Ubiquitinated by the SCF(SKP2) complex, leading to its degradation. |
| Function | Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability. M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing. Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT and ribonuclease P/MRP complexes, depending on the context. The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation. M6A-containing mRNAs containing a binding site for RIDA/HRSP12 (5'-GGUUC-3') are preferentially degraded by endoribonucleolytic cleavage: cooperative binding of RIDA/HRSP12 and YTHDF2 to transcripts leads to recruitment of the ribonuclease P/MRP complex. Other m6A-containing mRNAs undergo deadenylation via direct interaction between YTHDF2 and CNOT1, leading to recruitment of the CCR4-NOT and subsequent deadenylation of m6A-containing mRNAs. Required maternally to regulate oocyte maturation: probably acts by binding to m6A-containing mRNAs, thereby regulating maternal transcript dosage during oocyte maturation, which is essential for the competence of oocytes to sustain early zygotic development. Also required during spermatogenesis: regulates spermagonial adhesion by promoting degradation of m6A-containing transcripts coding for matrix metallopeptidases. Also involved in hematopoietic stem cells specification by binding to m6A-containing mRNAs, leading to promote their degradation. Also acts as a regulator of neural development by promoting m6A-dependent degradation of neural development-related mRNA targets. Inhibits neural specification of induced pluripotent stem cells by binding to methylated neural-specific mRNAs and promoting their degradation, thereby restraining neural differentiation. Regulates circadian regulation of hepatic lipid metabolism: acts by promoting m6A-dependent degradation of PPARA transcripts. Regulates the innate immune response to infection by inhibiting the type I interferon response: acts by binding to m6A-containing IFNB transcripts and promoting their degradation. May also act as a promoter of cap-independent mRNA translation following heat shock stress: upon stress, relocalizes to the nucleus and specifically binds mRNAs with some m6A methylation mark at their 5'-UTR, protecting demethylation of mRNAs by FTO, thereby promoting cap-independent mRNA translation. Regulates mitotic entry by promoting the phase-specific m6A-dependent degradation of WEE1 transcripts. 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. The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules. May also recognize and bind RNAs modified by C5-methylcytosine (m5C) and act as a regulator of rRNA processing. |
| Protein Name | Yth Domain-Containing Family Protein 2 |
| Cellular Localisation | CytoplasmCytosolP-BodyStress GranuleNucleusLocalizes To The Cytosol And Relocates To The Nucleus Following Heat Shock StressCan Partition Into Different Structures: Into P-Bodies In Unstressed CellsAnd Into Stress Granules During Stress |
| Alternative Protein Names | Yth Domain-Containing Family Protein 2 proteinYthdf2 protein |
Information sourced from Uniprot.org
