PT - JOURNAL ARTICLE AU - Nazife Tolay AU - Alexander Buchberger TI - Comparative profiling of stress granule clearance reveals differential contributions of the ubiquitin system AID - 10.26508/lsa.202000927 DP - 2021 May 01 TA - Life Science Alliance PG - e202000927 VI - 4 IP - 5 4099 - https://www.life-science-alliance.org/content/4/5/e202000927.short 4100 - https://www.life-science-alliance.org/content/4/5/e202000927.full SO - Life Sci. Alliance2021 May 01; 4 AB - Stress granules (SGs) are cytoplasmic condensates containing untranslated mRNP complexes. They are induced by various proteotoxic conditions such as heat, oxidative, and osmotic stress. SGs are believed to protect mRNPs from degradation and to enable cells to rapidly resume translation when stress conditions subside. SG dynamics are controlled by various posttranslational modifications, but the role of the ubiquitin system has remained controversial. Here, we present a comparative analysis addressing the involvement of the ubiquitin system in SG clearance. Using high-resolution immunofluorescence microscopy, we found that ubiquitin associated to varying extent with SGs induced by heat, arsenite, H2O2, sorbitol, or combined puromycin and Hsp70 inhibitor treatment. SG-associated ubiquitin species included K48- and K63-linked conjugates, whereas free ubiquitin was not significantly enriched. Inhibition of the ubiquitin activating enzyme, deubiquitylating enzymes, the 26S proteasome and p97/VCP impaired the clearance of arsenite- and heat-induced SGs, whereas SGs induced by other stress conditions were little affected. Our data underline the differential involvement of the ubiquitin system in SG clearance, a process important to prevent the formation of disease-linked aberrant SGs.