Reactive sulfur species regulate tRNA methylthiolation and contribute to insulin secretion

Nozomu Takahashi, Fan Yan Wei, Sayaka Watanabe, Mayumi Hirayama, Yuya Ohuchi, Atsushi Fujimura, Taku Kaitsuka, Isao Ishii, Tomohiro Sawa, Hideki Nakayama, Takaaki Akaike, Kazuhito Tomizawa

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


The 2-methylthio (ms2) modification at A37 of tRNAs is critical for accurate decoding, and contributes to metabolic homeostasis in mammals. However, the regulatory mechanism of ms2 modification remains largely unknown. Here, we report that cysteine hydropersulfide (CysSSH), a newly identified reactive sulfur species, is involved in ms2 modification in cells. The suppression of intracellular CysSSH production rapidly reduced ms2 modification, which was rescued by the application of an exogenous CysSSH donor. Using a unique and stable isotope-labeled CysSSH donor, we show that CysSSH was capable of specifically transferring its reactive sulfur atom to the cysteine residues of ms2-modifying enzymes as well as ms2 modification. Furthermore, the suppression of CysSSH production impaired insulin secretion and caused glucose intolerance in both a pancreatic β-cell line and mouse model. These results demonstrate that intracellular CysSSH is a novel sulfur source for ms2 modification, and that it contributes to insulin secretion.

Original languageEnglish
Pages (from-to)435-445
Number of pages11
JournalNucleic Acids Research
Issue number1
Publication statusPublished - 2017 Jan 9


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