Abstract
Spatial organization of cellular processes in membranous or membrane-less organelles (MLOs, alias molecular condensates) is a key concept for compartmentalizing biochemical pathways. Prime examples of MLOs are the nucleolus, PML nuclear bodies, nuclear splicing speckles or cytosolic stress granules. They all represent distinct sub-cellular structures typically enriched in intrinsically disordered proteins and/or RNA and are formed in a process driven by liquid-liquid phase separation. Several MLOs are critically involved in proteostasis and their formation, disassembly and composition are highly sensitive to proteotoxic insults. Changes in the dynamics of MLOs are a major driver of cell dysfunction and disease. There is growing evidence that post-translational modifications are critically involved in controlling the dynamics and composition of MLOs and recent evidence supports an important role of the ubiquitin-like SUMO system in regulating both the assembly and disassembly of these structures. Here we will review our current understanding of SUMO function in MLO dynamics under both normal and pathological conditions.
Highlights
Most cellular processes are compartmentalized in membranous or membrane-less organelles (MLOs, termed molecular condensates)
We further found that impairment of the SUMO-targeted ubiquitin ligase (StUbL) pathway by chemical or genetic inhibition of SUMO2/3 or depletion of RNF4 significantly delays stress granules (SGs) clearance in cells recovering from heat or arsenite-induced proteotoxic stress
The role of SUMO in controlling MLO dynamics likely goes beyond the above-mentioned examples, since formation of Cajal bodies, processing bodies (P-bodies, PBs) and the recently described NELF bodies are controlled by SUMOylation
Summary
Most cellular processes are compartmentalized in membranous or membrane-less organelles (MLOs, termed molecular condensates). There are multiple examples, where SUMO-SIM interactions can function in a "glue-like" manner to control the assembly of protein complexes (Matunis et al, 2006). Under proteotoxic stress SUMO-primed ubiquitylation by RNF4 contributes to protein quality control by degrading misfolded nuclear proteins (Gartner and Muller, 2014; Guo et al, 2014).
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