A guide to membraneless organelles and their various roles in gene regulation

Membraneless organelles (MLOs) are detected in cells as dots of Introduction mesoscopic size. By undergoing phase separation into a liquid-like Features of membraneless or gel-like phase, MLOs contribute to intracellular compartmental- organelles ization of specific biological functions. In eukaryotes, dozens of MLOs Functions of membraneless have been identified, including the nucleolus, Cajal bodies, nuclear organelles speckles, paraspeckles, promyelocytic leukaemia protein (PML) Inter-organelle crosstalk nuclear bodies, nuclear stress bodies, processing bodies (P bodies) Membraneless organelles in and stress granules. MLOs contain specific proteins, of which many disease possess intrinsically disordered regions (1DRs), and nucleic acids, Emerging topics for future mainly RNA. Many MLOs contribute to gene regulation by different study mechanisms. Through sequestration of specific factors, MLOs promote biochemical reactions by simultaneously concentrating substrates and enzymes, and/or suppressing the activity of the sequestered factors elsewhere in the cell. Other MLOs construct inter-chromosomal hubs by associating with multiple loci, thereby contributing to the biogenesis of macromolecular machineries essential for gene expression, such as ribosomes and spliceosomes. The organization of many MLOs includes layers, which might have different biophysical properties and functions. MLOs are functionally interconnected and are involved in various diseases, prompting the emergence of therapeutics targeting them. In this Review, we introduce MLOs that are relevant to gene regulation and discuss their assembly, internal structure, gene-regulatory roles in transcription, RNA processing and translation, particularly in stress conditions, and their disease relevance.