Open AccessAcetylation-mediated remodeling of the nucleolus regulates cellular acetyl-CoA responses
Author(s) -
Ryan Houston,
Shiori Sekine,
Michael Calderon,
Fayaz Seifuddin,
Guanghui Wang,
Hiroyuki Kawagishi,
Daniela Malide,
Yuesheng Li,
Marjan Guček,
Mehdi Pirooznia,
Alissa J. Nelson,
Matthew P. Stokes,
Jacob Stewart-Ornstein,
Steven J. Mullett,
Stacy G. Wendell,
Simon C. Watkins,
Toren Finkel,
Yusuke Sekine
Publication year - 2020
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3000981
Subject(s) - nucleolus , biology , acetylation , histone , acetyl coa , microbiology and biotechnology , ribosomal protein , coenzyme a , ribosomal rna , biochemistry , rna , cytoplasm , gene , ribosome , metabolism , enzyme , reductase
The metabolite acetyl-coenzyme A (acetyl-CoA) serves as an essential element for a wide range of cellular functions including adenosine triphosphate (ATP) production, lipid synthesis, and protein acetylation. Intracellular acetyl-CoA concentrations are associated with nutrient availability, but the mechanisms by which a cell responds to fluctuations in acetyl-CoA levels remain elusive. Here, we generate a cell system to selectively manipulate the nucleo-cytoplasmic levels of acetyl-CoA using clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing and acetate supplementation of the culture media. Using this system and quantitative omics analyses, we demonstrate that acetyl-CoA depletion alters the integrity of the nucleolus, impairing ribosomal RNA synthesis and evoking the ribosomal protein-dependent activation of p53. This nucleolar remodeling appears to be mediated through the class IIa histone deacetylases (HDACs). Our findings highlight acetylation-mediated control of the nucleolus as an important hub linking acetyl-CoA fluctuations to cellular stress responses.