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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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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. |
format | Online Article Text |
id | pubmed-6182161 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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