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.