RNA Modifications Modulate Biomolecular Condensates in Stress and Disease.

Biomolecular condensates are dynamic membraneless organelles composed of proteins and RNAs that assemble through multivalent interactions and provide cells with powerful means to regulate gene expression in space and time. Different epitranscriptomic marks such as m6A, m1A, and m5C can reshape RNA structure-binding interfaces and multivalency and, in this manner, tuning which transcripts nucleate or partition into specific condensates and influencing their material state. This review summarizes how individual RNA modifications and their associated proteins regulate the formation and function of BMCs such as stress granules, P-bodies, nuclear bodies and disease-linked condensates in cancer and neurodegeneration. It highlights emerging concepts of combinatorial "epitranscriptomic codes" and bidirectional feedback between condensates and RNA-modifying enzymes and discusses the current experimental and technical gaps that still limit our understanding of modification crosstalk and condensate topology.