C20orf21, YTH domain-containing family protein 1, Dermatomyositis associated with cancer putative autoantigen 1, DACA-1
N6-methyladenosine (m6A) is an abundant RNA modification that plays an important role in mRNA splicing, processing, and stability. The m6A modification is specifically recognized by members of the YT521B homology (YTH) domain-containing family (YTHDF), consisting of YTHDF1, YTHDF2, and YTHDF3. All three members of the YTHDF family are primarily cytosolic proteins that share similar sequence and domain structure, including a conserved C-terminal YTH domain that specifically interacts with m6A. Despite these similarities, recent studies suggest that YTHDF proteins are involved in distinct regulatory functions with minimal overlap. Specifically, YTHDF1 binding has been reported to promote enhanced mRNA translation, but has no measurable effect on mRNA stability. Conversely, YTHDF2 binding appears to promote mRNA degradation, but has minimal effect on translation efficiency. The function of YTHDF3 is less clear, but it has been proposed to function as an auxiliary protein for both YTHDF1 and YTHDF2, helping to promote either increased mRNA translation or decay, respectively. Additional studies offer a different viewpoint, suggesting that all three YTHDF proteins initiate mRNA degradation, or mediate increased mRNA stability and protein expression, promoting the idea that these proteins may carry out similar rather than distinct functions.
