Open Accessm6A-binding YTHDF proteins promote stress granule formation
Author(s) -
Ye Fu,
Xiaowei Zhuang
Publication year - 2020
Publication title -
nature chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.412
H-Index - 216
eISSN - 1552-4469
pISSN - 1552-4450
DOI - 10.1038/s41589-020-0524-y
Subject(s) - stress granule , rna binding protein , microbiology and biotechnology , chemistry , granule (geology) , p bodies , biophysics , rna , messenger rna , biology , biochemistry , gene , translation (biology) , paleontology
Diverse RNAs and RNA-binding proteins form phase-separated, membraneless granules in cells under stress conditions. However, the role of the prevalent mRNA methylation, m 6 A, and its binding proteins in stress granule (SG) assembly remain unclear. Here, we show that m 6 A-modified mRNAs are enriched in SGs, and that m 6 A-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 m 6 A-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 the junctions between SG core clusters, and potentially promote SG formation by reducing the activation energy barrier and critical size for SG condensate formation. Our results suggest a new function of the m 6 A-binding YTHDF proteins in regulating SG formation.