A Unified Model for the Function of YTHDF Proteins in Regulating m6A-Modified mRNA
By S. Zaccara, Samie R. Jaffrey. Cell, 2020
670 citations recorded by the source corpus.
Summary N6-methyladenosine (m6A) is the most abundant mRNA nucleotide modification and regulates critical aspects of cellular physiology and differentiation. m6A is thought to mediate its effects through a complex network of interactions between different m6A sites and three functionally distinct cytoplasmic YTHDF m6A-binding proteins (DF1, DF2, and DF3). In contrast to the prevailing model, we show that DF proteins bind the same m6A-modified mRNAs, rather than different mRNAs. Furthermore, we find that DF proteins do not induce translation in HeLa cells. Instead, the DF paralogs act redundantly to mediate mRNA degradation and cellular differentiation. The ability of DF proteins to regulate stability and differentiation becomes evident only when all three DF paralogs are simultaneously depleted. Our studies reveal a unified model of m6A function in which all m6A-modified mRNAs are subjected to the combined action of the YTHDF proteins in proportion to the number of m6A sites.
Subfields: Electrical and Electronic Engineering, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/71c12cdc4f09b0ccc449471b12c5df9c37f95a36
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Citations in the corpus
- m6A RNA methylation: from mechanisms to therapeutic potential (2021, positive): “…mechanisms and underlining the need for future studies to fully unravel the molecular details, is the fact that two recent studies have proposed that YTHDF proteins function more similarly in the regulation of gene expression than previously described (Lasman et al , 2020; Zaccara & Jaffrey, 2020).”