YTHDF3
Description
The YTHDF3 (YTH N6-methyladenosine RNA binding protein F3) is a protein-coding gene located on chromosome 8.
YTH domain family protein 3 is a protein that in humans is encoded by the YTHDF3 gene.
YTHDF3 specifically binds to N6-methyladenosine (m6A) modified RNA molecules, which are present in internal sites of mRNAs and some non-coding RNAs, and regulates their stability. M6A plays a key role in mRNA stability and processing. YTHDF3 promotes degradation of m6A-containing mRNAs via interaction with the CCR4-NOT complex or PAN3. The YTHDF family members (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNA targets and act redundantly to mediate mRNA degradation and cellular differentiation. YTHDF3 is a negative regulator of type I interferon response by down-regulating interferon-stimulated genes (ISGs) expression by binding to FOXO3 mRNAs independently of METTL3-mediated m6A modification. YTHDF3 also cooperates with YTHDF2 to regulate mRNA stability by promoting degradation of m6A-containing mRNAs. YTHDF3 binds to m6A-containing circular RNAs (circRNAs) that are generated through back-splicing of pre-mRNAs. YTHDF3 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. YTHDF3 may also recognize and bind N1-methyladenosine (m1A)-containing mRNAs, and inhibits trophoblast invasion by binding to m1A-methylated transcripts of IGF1R, promoting their degradation. YTHDF3 exhibits antiviral activity against HIV-1 virus by incorporating into HIV-1 particles in a nucleocapsid-dependent manner and reduces viral infectivity. YTHDF3 may interfere with the early steps of the viral life cycle by binding to N6-methyladenosine (m6A) modified sites on the HIV-1 RNA genome. YTHDF3 interacts with CNOT1, promoting recruitment of the CCR4-NOT complex. It also interacts with YTHDF1 and YTHDF2.
YTHDF3 is also known as DF3.
