A Unified Model for the Function of YTHDF Proteins in Regulating MA-Modified MRNA

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2020 Jun 4

PMID 32492408

Citations 357

Authors

Sara Zaccara

Samie R Jaffrey

Affiliations

Soon will be listed here.

Abstract

N-methyladenosine (mA) is the most abundant mRNA nucleotide modification and regulates critical aspects of cellular physiology and differentiation. mA is thought to mediate its effects through a complex network of interactions between different mA sites and three functionally distinct cytoplasmic YTHDF mA-binding proteins (DF1, DF2, and DF3). In contrast to the prevailing model, we show that DF proteins bind the same mA-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 depleted simultaneously. Our study reveals a unified model of mA function in which all mA-modified mRNAs are subjected to the combined action of YTHDF proteins in proportion to the number of mA sites.

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