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EMBO Rep. 2018 Dec;19(12). pii: e46377. doi: 10.15252/embr.201846377. Epub 2018 Nov 12.

Arginine methylation of SIRT7 couples glucose sensing with mitochondria biogenesis.

Author information

1
Fudan University Shanghai Cancer Center, Cancer Metabolism Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
2
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
3
Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
4
State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
5
Fudan University Shanghai Cancer Center, Cancer Metabolism Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China yiping_wang@fudan.edu.cn.

Abstract

Sirtuins (SIRTs) are a class of lysine deacylases that regulate cellular metabolism and energy homeostasis. Although sirtuins have been proposed to function in nutrient sensing and signaling, the underlying mechanism remains elusive. SIRT7, a histone H3K18-specific deacetylase, epigenetically controls mitochondria biogenesis, ribosomal biosynthesis, and DNA repair. Here, we report that SIRT7 is methylated at arginine 388 (R388), which inhibits its H3K18 deacetylase activity. Protein arginine methyltransferase 6 (PRMT6) directly interacts with and methylates SIRT7 at R388 in vitro and in vivo R388 methylation suppresses the H3K18 deacetylase activity of SIRT7 without modulating its subcellular localization. PRMT6-induced H3K18 hyperacetylation at SIRT7-target gene promoter epigenetically promotes mitochondria biogenesis and maintains mitochondria respiration. Moreover, high glucose enhances R388 methylation in mouse fibroblasts and liver tissue. PRMT6 signals glucose availability to SIRT7 in an AMPK-dependent manner. AMPK induces R388 hypomethylation by disrupting the association between PRMT6 and SIRT7. Together, PRMT6-induced arginine methylation of SIRT7 coordinates glucose availability with mitochondria biogenesis to maintain energy homeostasis. Our study uncovers the regulatory role of SIRT7 arginine methylation in glucose sensing and mitochondria biogenesis.

KEYWORDS:

PRMT6; SIRT7; arginine methylation; glucose sensing; mitochondria biogenesis

PMID:
30420520
PMCID:
PMC6280788
[Available on 2019-12-01]
DOI:
10.15252/embr.201846377

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