The acetylation of lysine-376 of G3BP1 regulates RNA binding and stress granule dynamics

Jozsef Gal, Jing Chen, Duck Young Na, Laura Tichacek, Kelly R. Barnett, Haining Zhu

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Stress granules (SGs) are ribonucleoprotein aggregates that form in response to stress conditions. The regulation of SG dynamics is not fully understood. Permanent pathological SG-like structures were reported in neurodegenerative diseases such as amyotrophic lateral sclerosis. The Ras GTPase-activating proteinbinding protein G3BP1 is a central regulator of SG dynamics. We found that the lysine 376 residue (K376) of G3BP1, which is in the RRM RNA binding domain, was acetylated. Consequently, G3BP1 RNA binding was impaired by K376 acetylation. In addition, the acetylation-mimicking mutation K376Q impaired the RNA-dependent interaction of G3BP1 with poly(A)-binding protein 1 (PABP1), but its RNA-independent interactions with caprin-1 and USP10 were little affected. The formation of G3BP1 SGs depended on G3BP1 RNA binding; thus, replacement of endogenous G3BP1 with the K376Q mutant or the RNA binding-deficient F380L/F382L mutant interfered with SG formation. Significant G3BP1 K376 acetylation was detected during SG resolution, and K376-acetylated G3BP1 was seen outside SGs. G3BP1 acetylation is regulated by histone deacetylase 6 (HDAC6) and CBP/p300. Our data suggest that the acetylation of G3BP1 facilitates the disassembly of SGs, offering a potential avenue to mitigate hyperactive stress responses under pathological conditions.

Original languageEnglish (US)
Article numbere00052-19
JournalMolecular and cellular biology
Volume39
Issue number22
DOIs
StatePublished - Nov 2019
Externally publishedYes

Keywords

  • Acetylation
  • CBP/p300
  • G3BP1
  • HDAC6
  • Stress granule
  • Stress proteins
  • Stress response

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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