Modulation of Phase Separation by RNA: A Glimpse on N⁶-Methyladenosine Modification

Phase separation is the driving force behind formation of various biomolecular condensates (BioMCs), which sub-compartmentalize certain cellular components in a membraneless manner to orchestrate numerous biological processes. Many BioMCs are composed of proteins and RNAs. While the features and functions of proteins are well studied, less attention was paid to the other essential component RNAs. Here, we describe how RNA contributes to the biogenesis, dissolution, and properties of BioMCs as a multivalence providing scaffold for proteins/RNA to undergo phase separation. Specifically, we focus on N⁶-methyladenosine (m⁶A), the most widely distributed dynamic post-transcriptional modification, which would change the charge, conformation, and RNA-binding protein (RBP) anchoring of modified RNA. m⁶A RNA-modulated phase separation is a new perspective to illustrate m⁶A-mediated various biological processes. We summarize m⁶A main functions as "beacon" to recruit reader proteins and "structural switcher" to alter RNA-protein and RNA-RNA interactions to modulate phase separation and regulate the related biological processes.