Protein: YTH domain-containing family protein 2 (Q91YT7)
Organism: Mus musculus (Mouse)
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 (By similarity). 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 (By similarity). Regulates circadian regulation of hepatic lipid metabolism: acts by promoting m6A-dependent degradation of PPARA transcripts (By similarity). 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 (By similarity). Regulates mitotic entry by promoting the phase-specific m6A-dependent degradation of WEE1 transcripts (By similarity). 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). May also recognize and bind RNAs modified by C5-methylcytosine (m5C) and act as a regulator of rRNA processing (By similarity).
Subcellular location: Cytoplasm, cytosol {ECO:0000305|PubMed:28867294, ECO:0000305|PubMed:32943573}. Cytoplasm, P-body {ECO:0000250|UniProtKB:Q9Y5A9}. Cytoplasm, Stress granule {ECO:0000250|UniProtKB:Q9Y5A9}. Nucleus {ECO:0000269|PubMed:32943573}. 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}.
Interaction partners:
- 2-iminobutanoate/2-iminopropanoate deaminase
- CCR4-NOT transcription complex subunit 1
- N
- N
- YTH domain-containing family protein 3
- Pre-mRNA-splicing regulator WTAP
- RNA demethylase ALKBH5
- Alpha-ketoglutarate-dependent dioxygenase FTO
- Protein virilizer homolog
- Fragile X messenger ribonucleoprotein 1
Sequence:
MSASSLLEQRPKGQGNKVQNGSVHQKDGLNDDDFEPYLSPQARPNNAYTAMSDSYLPSYYSPSIGFSYSLGEAAWSTGGDTAMPYLTSYGQLSNGEPHFLPDAMFGQPGALGSTPFLGQHGFNFFPSGIDFSAWGNNSSQGQSTQSSGYSSNYAYAPSSLGGAMIDGQSAFANETLNKAPGMNTIDQGMAALKLGSTEVASSVPKVVGSAVGSGSITSNIVASSSLPPATIAPPKPASWADIASKPAKQQPKLKTKNGIAGSSLPPPPIKHNMDIGTWDNKGPVAKAPSQALVQNIGQPTQGSPQPVGQQANNSPPVAQASVGQQTQPLPPPPPQPAQLSVQQQAAQPTRWVAPRNRGSGFGHNGVDGNGVGQSQAGSGSTPSEPHPVLEKLRSINNYNPKDFDWNLKHGRVFIIKSYSEDDIHRSIKYNIWCSTEHGNKRLDAAYRSMNGKGPVYLLFSVNGSGHFCGVAEMKSAVDYNTCAGVWSQDKWKGRFDVRWIFVKDVPNSQLRHIRLENNENKPVTNSRDTQEVPLEKAKQVLKIIASYKHTTSIFDDFSHYEKRQEEEESVKKERQGRGK