Recent advances in the interplay between stress granules and m6A RNA modification

Abstract

Stress granules (SGs) are non-membranous organelles driven by the liquid–liquid phase separation (LLPS) of RNA and RNA-binding proteins under various stress conditions. LLPS is mediated by multivalent interactions and affected by RNA modifications and their binders. Most neurodegenerative disease (ND)-related proteins, including TDP-43, FUS, Tau, and TIA1, are components of SGs, indicating the involvement of SGs in ND initiation or progression. Recent studies have reported the enrichment of N6-methyladenosine (m6A)-modified RNA and its corresponding reader proteins in SGs and the abnormal deposition of m6A-modified RNA in ND. Therefore, there is urgent to determine the crosstalk and underlying mechanisms between m6A modification and SGs. The main questions that must be answered are as follows: (1) Which reader participates in m6A enrichment in SGs? (2) What is the role of m6A modification in SG formation? How does it promote LLPS? (3) What is the role of SGs in regulating the fate of m6A-modified RNA? (4) Does the interplay between SGs and m6A modification contribute to chronic diseases such as ND? Therefore, based on these questions, we summarized recently published literature and tried to provide a comprehensive view of the interplay between SGs and m6A modification and their contribution to ND.