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Deacetylation of NAT10 by Sirt1 promotes the transition from rRNA biogenesis to autophagy upon energy stress

Anabolism and catabolism are tightly regulated according to the cellular energy supply. Upon energy stress, ribosomal RNA (rRNA) biogenesis is inhibited, and autophagy is induced. However, the mechanism linking rRNA biogenesis and autophagy is unclear. Here, we demonstrate that the nucleolar protein...

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Autores principales: Liu, Xiaofeng, Cai, Shiying, Zhang, Chunfeng, Liu, Zhenzhen, Luo, Jianyuan, Xing, Baocai, Du, Xiaojuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182161/
https://www.ncbi.nlm.nih.gov/pubmed/30165671
http://dx.doi.org/10.1093/nar/gky777
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author Liu, Xiaofeng
Cai, Shiying
Zhang, Chunfeng
Liu, Zhenzhen
Luo, Jianyuan
Xing, Baocai
Du, Xiaojuan
author_facet Liu, Xiaofeng
Cai, Shiying
Zhang, Chunfeng
Liu, Zhenzhen
Luo, Jianyuan
Xing, Baocai
Du, Xiaojuan
author_sort Liu, Xiaofeng
collection PubMed
description Anabolism and catabolism are tightly regulated according to the cellular energy supply. Upon energy stress, ribosomal RNA (rRNA) biogenesis is inhibited, and autophagy is induced. However, the mechanism linking rRNA biogenesis and autophagy is unclear. Here, we demonstrate that the nucleolar protein NAT10 plays a role in the transition between rRNA biogenesis and autophagy. Under normal conditions, NAT10 is acetylated to activate rRNA biogenesis and inhibit autophagy induction. Mechanistic studies demonstrate that NAT10 binds to and acetylates the autophagy regulator Che-1 at K228 to suppress the Che-1-mediated transcriptional activation of downstream genes Redd1 and Deptor under adequate energy supply conditions. Upon energy stress, NAT10 is deacetylated by Sirt1, leading to suppression of NAT10-activated rRNA biogenesis. In addition, deacetylation of NAT10 abolishes the NAT10-mediated transcriptional repression of Che-1, leading to the release of autophagy inhibition. Collectively, we demonstrate that the acetylation status of NAT10 is important for the anabolism-catabolism transition in response to energy stress, providing a novel mechanism by which nucleolar proteins control rRNA synthesis and autophagy in response to the cellular energy supply.
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spelling pubmed-61821612018-10-18 Deacetylation of NAT10 by Sirt1 promotes the transition from rRNA biogenesis to autophagy upon energy stress Liu, Xiaofeng Cai, Shiying Zhang, Chunfeng Liu, Zhenzhen Luo, Jianyuan Xing, Baocai Du, Xiaojuan Nucleic Acids Res Molecular Biology Anabolism and catabolism are tightly regulated according to the cellular energy supply. Upon energy stress, ribosomal RNA (rRNA) biogenesis is inhibited, and autophagy is induced. However, the mechanism linking rRNA biogenesis and autophagy is unclear. Here, we demonstrate that the nucleolar protein NAT10 plays a role in the transition between rRNA biogenesis and autophagy. Under normal conditions, NAT10 is acetylated to activate rRNA biogenesis and inhibit autophagy induction. Mechanistic studies demonstrate that NAT10 binds to and acetylates the autophagy regulator Che-1 at K228 to suppress the Che-1-mediated transcriptional activation of downstream genes Redd1 and Deptor under adequate energy supply conditions. Upon energy stress, NAT10 is deacetylated by Sirt1, leading to suppression of NAT10-activated rRNA biogenesis. In addition, deacetylation of NAT10 abolishes the NAT10-mediated transcriptional repression of Che-1, leading to the release of autophagy inhibition. Collectively, we demonstrate that the acetylation status of NAT10 is important for the anabolism-catabolism transition in response to energy stress, providing a novel mechanism by which nucleolar proteins control rRNA synthesis and autophagy in response to the cellular energy supply. Oxford University Press 2018-10-12 2018-08-28 /pmc/articles/PMC6182161/ /pubmed/30165671 http://dx.doi.org/10.1093/nar/gky777 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Molecular Biology
Liu, Xiaofeng
Cai, Shiying
Zhang, Chunfeng
Liu, Zhenzhen
Luo, Jianyuan
Xing, Baocai
Du, Xiaojuan
Deacetylation of NAT10 by Sirt1 promotes the transition from rRNA biogenesis to autophagy upon energy stress
title Deacetylation of NAT10 by Sirt1 promotes the transition from rRNA biogenesis to autophagy upon energy stress
title_full Deacetylation of NAT10 by Sirt1 promotes the transition from rRNA biogenesis to autophagy upon energy stress
title_fullStr Deacetylation of NAT10 by Sirt1 promotes the transition from rRNA biogenesis to autophagy upon energy stress
title_full_unstemmed Deacetylation of NAT10 by Sirt1 promotes the transition from rRNA biogenesis to autophagy upon energy stress
title_short Deacetylation of NAT10 by Sirt1 promotes the transition from rRNA biogenesis to autophagy upon energy stress
title_sort deacetylation of nat10 by sirt1 promotes the transition from rrna biogenesis to autophagy upon energy stress
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182161/
https://www.ncbi.nlm.nih.gov/pubmed/30165671
http://dx.doi.org/10.1093/nar/gky777
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