José M Liboy-Lugo, Carla A Espinoza, Jessica Sheu-Gruttadauria, Jesslyn E Park, Albert Xu, Ziad Jowhar, Angela L Gao, José A Carmona-Negrón, Torsten Wittmann, Natalia Jura, Stephen N Floor
{"title":"在细胞应激过程中,G3BP 同工酶会对应激颗粒的组装和基因表达产生不同影响。","authors":"José M Liboy-Lugo, Carla A Espinoza, Jessica Sheu-Gruttadauria, Jesslyn E Park, Albert Xu, Ziad Jowhar, Angela L Gao, José A Carmona-Negrón, Torsten Wittmann, Natalia Jura, Stephen N Floor","doi":"10.1091/mbc.E24-02-0062","DOIUrl":null,"url":null,"abstract":"<p><p>Stress granules (SGs) are macromolecular assemblies that form under cellular stress. Formation of these membraneless organelles is driven by the condensation of RNA and RNA-binding proteins such as G3BPs. G3BPs form SGs following stress-induced translational arrest. Three G3BP paralogues (G3BP1, G3BP2A, and G3BP2B) have been identified in vertebrates. However, the contribution of different G3BP paralogues to SG formation and gene expression changes is incompletely understood. Here, we probed the functions of G3BPs by identifying important residues for SG assembly at their N-terminal domain such as V11. This conserved amino acid is required for formation of the G3BP-Caprin-1 complex, hence promoting SG assembly. Total RNA sequencing and ribosome profiling revealed that a G3BP<sup>V11A</sup> mutant leads to changes in mRNA levels and ribosome engagement during the integrated stress response (ISR). Moreover, we found that G3BP2B preferentially forms SGs and promotes changes in mRNA expression under endoplasmic reticulum (ER) stress. Furthermore, our work is a resource for researchers to study gene expression changes under cellular stress. Together, this work suggests that perturbing protein-protein interactions mediated by G3BPs affect SG assembly and gene expression during the ISR, and such functions are differentially regulated by G3BP paralogues under ER stress.</p>","PeriodicalId":18735,"journal":{"name":"Molecular Biology of the Cell","volume":" ","pages":"ar140"},"PeriodicalIF":3.1000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617104/pdf/","citationCount":"0","resultStr":"{\"title\":\"G3BP isoforms differentially affect stress granule assembly and gene expression during cellular stress.\",\"authors\":\"José M Liboy-Lugo, Carla A Espinoza, Jessica Sheu-Gruttadauria, Jesslyn E Park, Albert Xu, Ziad Jowhar, Angela L Gao, José A Carmona-Negrón, Torsten Wittmann, Natalia Jura, Stephen N Floor\",\"doi\":\"10.1091/mbc.E24-02-0062\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Stress granules (SGs) are macromolecular assemblies that form under cellular stress. Formation of these membraneless organelles is driven by the condensation of RNA and RNA-binding proteins such as G3BPs. G3BPs form SGs following stress-induced translational arrest. Three G3BP paralogues (G3BP1, G3BP2A, and G3BP2B) have been identified in vertebrates. However, the contribution of different G3BP paralogues to SG formation and gene expression changes is incompletely understood. Here, we probed the functions of G3BPs by identifying important residues for SG assembly at their N-terminal domain such as V11. This conserved amino acid is required for formation of the G3BP-Caprin-1 complex, hence promoting SG assembly. Total RNA sequencing and ribosome profiling revealed that a G3BP<sup>V11A</sup> mutant leads to changes in mRNA levels and ribosome engagement during the integrated stress response (ISR). Moreover, we found that G3BP2B preferentially forms SGs and promotes changes in mRNA expression under endoplasmic reticulum (ER) stress. Furthermore, our work is a resource for researchers to study gene expression changes under cellular stress. 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G3BP isoforms differentially affect stress granule assembly and gene expression during cellular stress.
Stress granules (SGs) are macromolecular assemblies that form under cellular stress. Formation of these membraneless organelles is driven by the condensation of RNA and RNA-binding proteins such as G3BPs. G3BPs form SGs following stress-induced translational arrest. Three G3BP paralogues (G3BP1, G3BP2A, and G3BP2B) have been identified in vertebrates. However, the contribution of different G3BP paralogues to SG formation and gene expression changes is incompletely understood. Here, we probed the functions of G3BPs by identifying important residues for SG assembly at their N-terminal domain such as V11. This conserved amino acid is required for formation of the G3BP-Caprin-1 complex, hence promoting SG assembly. Total RNA sequencing and ribosome profiling revealed that a G3BPV11A mutant leads to changes in mRNA levels and ribosome engagement during the integrated stress response (ISR). Moreover, we found that G3BP2B preferentially forms SGs and promotes changes in mRNA expression under endoplasmic reticulum (ER) stress. Furthermore, our work is a resource for researchers to study gene expression changes under cellular stress. Together, this work suggests that perturbing protein-protein interactions mediated by G3BPs affect SG assembly and gene expression during the ISR, and such functions are differentially regulated by G3BP paralogues under ER stress.
期刊介绍:
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