RanBP2-dependent SUMOylation of G3BP2 inhibits formation, and promotes disassembly, of stress granules.

Stress granules and processing bodies (P-bodies) are dynamic cytoplasmic ribonucleoprotein (RNP) condensates that coordinate translation inhibition, mRNA storage, and decay during cellular stress. Emerging evidence suggests that SUMOylation contributes to the regulation of these RNP granules in human cells, though the underlying mechanisms remain largely unexplored. Here, we identify RanBP2-dependent SUMOylation as a key regulator of stress granule and P-body dynamics. Cells that lack RanBP2-mediated SUMOylation show enhanced stress granule assembly and delayed disassembly in response to oxidative stress. We further demonstrate that G3BP2, a core component of stress granules, is SUMOylated in a RanBP2-dependent manner at lysine 281, and that this modification limits spontaneous stress granule formation and promotes efficient disassembly. In addition, the loss of RanBP2-mediated SUMOylation reduces P-body abundance and promotes the merging of a subset of P-bodies with stress granules during stress. Together, our findings suggest that SUMOylation may regulate RNP granules by increasing G3BP solubility, thereby limiting stress granule formation, and by maintaining the balance and segregation of stress granules and P-bodies.