Advances in the phase separation-organized membraneless organelles in cells: a narrative review

Abstract: Membraneless organelles (MLOs) are micro-compartments that lack delimiting membranes, concentrating several macro-molecules with a high local concentration in eukaryotic cells. Recent studies have shown that MLOs have pivotal roles in multiple biological processes, including gene transcription, RNA metabolism, translation, protein modification, and signal transduction. These biological processes in cells have essential functions in many diseases, such as cancer, neurodegenerative diseases, and virus-related diseases. The liquid-liquid phase separation (LLPS) microenvironment within cells is thought to be the driving force for initiating the formation of micro-compartments with a liquid-like property, becoming an important organizing principle for MLOs to mediate organism responses. In this review, we comprehensively elucidated the formation of these MLOs and the relationship between biological functions and associated diseases. The mechanisms underlying the influence of protein concentration and valency on phase separation in cells are also discussed. MLOs undergoing the LLPS process have diverse functions, including stimulation of some adaptive and reversible responses to alter the transcriptional or translational processes, regulation of the concentrations of biomolecules in living cells, and maintenance of cell morphogenesis. Finally, we highlight that the development of this field could pave the way for developing novel therapeutic strategies for the treatment of LLPS-related diseases based on the understanding of phase separation in the coming years.