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SIRT1 Functions as a Negative Regulator of Eukaryotic Poly(A)RNA Transport.

Abstract
Most eukaryotic mRNAs are polyadenylated in the nucleus, and the poly(A)-tail is required for efficient mRNA export and translation. However, mechanisms governing mRNA transport remain unclear. Here, we report that the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1 acts as an energy sensor and negatively regulates poly(A)RNA transport via deacetylating a poly(A)-binding protein, PABP1. Upon energy starvation, SIRT1 interacts with and deacetylates PABP1 and deactivates its poly(A)RNA binding, leading to nuclear accumulation of PABP1 and poly(A)RNA and thus facilitating eukaryotic cells to attenuate protein synthesis and energy consumption to adapt to energy stress. Moreover, AMPK-directed SIRT1 phosphorylation is required for energy starvation-induced PABP1-SIRT1 association, PABP1 deacetylation, and poly(A)RNA nuclear retention. In addition, the SIRT1-PABP1 association is not specific to energy starvation but represents a common stress response. These observations provide insights into dynamic modulation of eukaryotic mRNA transport and translation, suggesting that the poly(A)-tail also provides a basis for eukaryotes to effectively shut down mature mRNA transport and thereby tailor protein synthesis to maintain energy homeostasis under stress conditions.
AuthorsPeipei Shan, Guangjian Fan, Lianhui Sun, Jinqin Liu, Weifang Wang, Chen Hu, Xiaohong Zhang, Qiwei Zhai, Xiaoyu Song, Liu Cao, Yongping Cui, Shengping Zhang, Chuangui Wang
JournalCurrent biology : CB (Curr Biol) Vol. 27 Issue 15 Pg. 2271-2284.e5 (Aug 07 2017) ISSN: 1879-0445 [Electronic] England
PMID28756945 (Publication Type: Journal Article)
CopyrightCopyright © 2017 Elsevier Ltd. All rights reserved.
Chemical References
  • Poly(A)-Binding Protein I
  • SIRT1 protein, human
  • Sirt1 protein, mouse
  • Sirtuin 1
Topics
  • Animals
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Knockout
  • Poly(A)-Binding Protein I (genetics, metabolism)
  • RNA Transport
  • Sirtuin 1 (genetics, metabolism)

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