Involvement of small molecules and metabolites in regulation of biomolecular condensate properties

Abstract

Biomolecular condensate (BMCs) formation facilitates the grouping of molecules, including proteins, nucleic acids, and small molecules, creating specific microenvironments with particular functions. They are often assembled through liquid-liquid phase separation (LLPS), a phenomenon that arises when specific proteins, nucleic acids, and small molecules demix from the aqueous environment into another phase with different physiochemical properties. BMCs assemble and disassemble in response to external and internal stimuli such as temperature, molecule concentration, ionic strength, pH, and cellular redox state. Likewise, the nature of the regulatory stimuli may affect the lifespan, morphology, and content of BMCs. In humans, compelling evidence points to the critical role of BMCs in diseases. By contrast, the link between BMC formation, stress resistance, and cell survival has not been revealed in plants. Recent studies have pointed out the nascent roles of small molecules in the assembly and dynamics of BMCs; however, this is still an emerging field of study. This review briefly highlights the most significant efforts to identify the molecular mechanisms between small molecules and BMC formation and regulation in plants and other organisms. We then discuss (i) how small molecules exert control over the BMC assembly and dynamics in plants and (ii) how small molecules can influence the formation and material properties of plant BMCs. Finally, we propose novel alternatives that might help to understand the relationship between chemicals and condensation dynamics and their possible application to plant biotechnology.

Keywords: Biomolecular condensates; Liquid–liquid phase separation; Metabolites; Small molecule.