| Abstract |
Stress granules (SGs) are membraneless ribonucleoprotein condensates that form under stress and dissolve during recovery. While assembly mechanisms are well characterized, the temporal organization of disassembly remains incompletely understood. Here, we performed time-resolved proximity proteomics across SG disassembly (0-50 min recovery; n = 3) using G3BP1 as bait, identifying 79 proteins with robust temporal dynamics. Unsupervised clustering resolved five kinetic modules: early-increase, early-decrease/late-increase, transient-drop at ∼40 min, early-decrease, and zig-zag patterns. The transient-drop module was enriched for RNA-processing factors, consistent with transient changes in RNA-processing factor engagement. SYNCRIP, an hnRNP family protein in the early-decrease/late-increase module, showed characteristic biphasic dynamics during recovery. Functional validation demonstrated that SYNCRIP knockdown specifically impairs late-phase SG clearance-increasing granule size at 50 min recovery-without affecting formation. Together, our data provide a modular temporal map of SG disassembly and establish SYNCRIP as a functionally validated factor required for late-phase clearance.
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