The role of phase separation in RNA modification: both cause and effect

Phase separation is a critical mechanism for partitioning cellular functions by specific aggregation of biological macromolecules. Recent studies have found that phase separation is widely contributed in various biological functions, particularly in RNA related processes. Over 170 different post-transcriptional modifications occur in RNA, which is considered to be one of the most important physiological and pathogenic epigenetic mechanisms. Here, we discuss the role of phase separation in regulating RNA modification processing to ensure orderly RNA metabolism and function. Enzymes responsible for RNA modification undergo compartmentalization, enabling them to traffic client RNAs and amplify modifying efficacy. Meanwhile, altered RNA affects the formation, dissolution, and biophysical properties of phase separation conversely. These findings deeper our understanding of the interplay between phase separation and RNAs that governs a wide range of cellular processes. Finally, we concluded pathological roles of phase separation in RNA modification towards clinical applications and outlined perspectives to research RNA modification through the lens of phase separation.