What are the distinguishing features and size requirements of biomolecular condensates and their implications for RNA-containing condensates?

ABSTRACT

Exciting recent work has highlighted that numerous cellular compartments lack encapsulating lipid bilayers (often called "membraneless organelles"), and that their structure and function are central to the regulation of key biological processes, including transcription, RNA splicing, translation, and more. These structures have been described as "biomolecular condensates" to underscore that biomolecules can be significantly concentrated in them. Many condensates, including RNA granules and processing bodies, are enriched in proteins and nucleic acids. Biomolecular condensates exhibit a range of material states from liquid- to gel-like, with the physical process of liquid-liquid phase separation implicated in driving or contributing to their formation. To date, in vitro studies of phase separation have provided mechanistic insights into the formation and function of condensates. However, the link between the often micron-sized in vitro condensates with nanometer-sized cellular correlates has not been well established. Consequently, questions have arisen as to whether cellular structures below the optical resolution limit can be considered biomolecular condensates. Similarly, the distinction between condensates and discrete dynamic hub complexes is debated. Here we discuss the key features that define biomolecular condensates to help understand behaviors of structures containing and generating RNA.