RNA granules: functional compartments or incidental condensates?

Abstract

In this review, Putnam et al. tackle our current understanding of RNA granules, intracellular phase-separated sites of RNA metabolism that contain factors for RNA biogenesis and turnover and are often assumed to represent specialized compartments for RNA biochemistry. The authors discuss the possibility that some RNA granules are condensation by-products that form when subsoluble RNP complexes saturate the cytoplasm or nucleoplasm, and introduce the term “incidental condensates” to refer to condensates that are tolerated by cells but do not add functionality beyond that provided by the soluble pool of saturating RNP complexes. Finally, they consider best practices for distinguishing functional RNA granules from incidental condensates.

Abstract

RNA granules are mesoscale assemblies that form in the absence of limiting membranes. RNA granules contain factors for RNA biogenesis and turnover and are often assumed to represent specialized compartments for RNA biochemistry. Recent evidence suggests that RNA granules assemble by phase separation of subsoluble ribonucleoprotein (RNP) complexes that partially demix from the cytoplasm or nucleoplasm. We explore the possibility that some RNA granules are nonessential condensation by-products that arise when RNP complexes exceed their solubility limit as a consequence of cellular activity, stress, or aging. We describe the use of evolutionary and mutational analyses and single-molecule techniques to distinguish functional RNA granules from “incidental condensates.”