M⁶A-binding YTHDF proteins promote stress granule formation.

ABSTRACT: Diverse RNAs and RNA-binding proteins form phase-separated, membraneless granules in cells under stress conditions. However, the role of the prevalent mRNA methylation, m⁶A, and its binding proteins in stress granule (SG) assembly remain unclear. Here, we show that m⁶A-modified mRNAs are enriched in SGs, and that m⁶A-binding YTHDF proteins are critical for SG formation. Depletion of YTHDF1/3 inhibits SG formation and recruitment of mRNAs to SGs. Both the N-terminal intrinsically disordered region and the C-terminal m⁶A-binding YTH domain of YTHDF proteins are important for SG formation. Super-resolution imaging further reveals that YTHDF proteins appear to be in a super-saturated state, forming clusters that often reside in the periphery of or at

SUBMITTER: Fu Y 

PROVIDER: S-EPMC7442727 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature