Dataset Information

Global profiling identifies a stress-responsive tyrosine site on EDC3 regulating biomolecular condensate formation

ABSTRACT: RNA granules are cytoplasmic condensates that organize biochemical and signaling complexes in response to cellular stress. Functional proteomic investigations under RNA granule-inducing conditions are needed to identify protein sites involved in coupling stress response with ribonucleoprotein regulation. Here, we apply chemical proteomics using sulfonyl-triazole (SuTEx) probes to capture cellular responses to oxidative and nutrient stress. The stress responsive tyrosine and lysine sites detected mapped to known proteins involved in processing body (PB) and stress granule (SG) pathways, including LSM14A, FUS, and EDC3. Notably, disruption of EDC3 tyrosine 475 (Y475) resulted in hypo-phosphorylation at S161 and S131, and altered protein-protein interactions (PPI) with decapping complex components (DDX6, DCP1A/B) and 14-3-3 proteins. This resulting mutant form of EDC3 was capable of rescuing the PB-deficient phenotype of EDC3 knockout cells. Taken together, our findings identify Y475 as an arsenic-responsive site that regulates RNA granule formation by coupling EDC3 post-translational modification and PPI states.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Dina Bai

LAB HEAD: Ku-Lung (Ken) Hsu

PROVIDER: PXD038010 | Pride | 2023-10-23

REPOSITORIES: pride

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Global profiling identifies a stress-responsive tyrosine site on EDC3 regulating biomolecular condensate formation.

Ciancone Anthony M AM Hosseinibarkooie Seyyedmohsen S Bai Dina L DL Borne Adam L AL Ferris Heather A HA Hsu Ku-Lung KL

Cell chemical biology 20221206 12

RNA granules are cytoplasmic condensates that organize biochemical and signaling complexes in response to cellular stress. Functional proteomic investigations under RNA-granule-inducing conditions are needed to identify protein sites involved in coupling stress response with ribonucleoprotein regulation. Here, we apply chemical proteomics using sulfonyl-triazole (SuTEx) probes to capture cellular responses to oxidative and nutrient stress. The stress-responsive tyrosine and lysine sites detected ...[more]

PMID: 36476517

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