Abstract
Lysine acetylation is a post-translational modification found on numerous proteins, a strategy used in cell signaling to change protein activity in response to internal or external cues. Sirtuin 1 (SIRT1) is a central lysine deacetylase involved in a variety of cellular processes including metabolism, apoptosis, and DNA repair. Here we characterize the lysine acetylome in mouse liver, and by using a model of Sirt1-/-knockout mouse, show that SIRT1 regulates the deacetylation of 70 proteins in the liver in-vivo. Amongst these SIRT1-regulated proteins, we find that four RNA-processing proteins and a chromatin-remodeling protein can be deacetylated by SIRT1 directly in-vitro. The discovery that SIRT1 has a potential role in RNA-processing suggests a new layer of regulation in the variety of functions performed by SIRT1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Animals
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Chromatin Assembly and Disassembly
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Gene Expression Regulation
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Gene Knockdown Techniques
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Liver / metabolism*
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Lysine / metabolism
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Mice
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RNA Processing, Post-Transcriptional*
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RNA, Messenger / metabolism*
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Sirtuin 1 / genetics
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Sirtuin 1 / metabolism*
Substances
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RNA, Messenger
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Sirt1 protein, mouse
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Sirtuin 1
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Lysine
Grants and funding
This work was supported by the Academic Center of Excellence Research Grant (No. 100019545) from GSK and the Industry Alignment Fund (IAF111002) from the Agency for Science, Technology and Research (A*STAR) of Singapore to F.X. Funding for the open-access charge was provided by A*STAR of Singapore. GSK provided the liver tissue from SIRT1 wild-type and knockout mice for this study. Other than that, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.