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Modified nucleoside triphosphates exist in mammals

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Abstract

DNA and RNA contain diverse chemical modifications that exert important influences in a variety of cellular processes. In addition to enzyme-mediated modifications of DNA and RNA, previous in vitro studies showed that pre-modified nucleoside triphosphates (NTPs) can be incorporated into DNA and RNA during replication and transcription. Herein, we established a chemical labeling method in combination with liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) analysis for the determination of endogenous NTPs in the mammalian cells and tissues. We synthesized 8-(diazomethyl)quinoline (8-DMQ) that could efficiently react with the phosphate group under mild condition to label NTPs. The developed method allowed sensitive detection of NTPs, with the detection limits improved by 56–137 folds. The results showed that 12 types of endogenous modified NTPs were distinctly determined in the mammalian cells and tissues. In addition, the majority of these modified NTPs exhibited significantly decreased contents in human hepatocellular carcinoma (HCC) tissues compared to tumor-adjacent normal tissues. Taken together, our study revealed the widespread existence of various modified NTPs in eukaryotes.

Graphical abstract: Modified nucleoside triphosphates exist in mammals

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Publication details

The article was received on 27 Dec 2017, accepted on 31 Mar 2018 and first published on 02 Apr 2018


Article type: Edge Article
DOI: 10.1039/C7SC05472F
Citation: Chem. Sci., 2018, Advance Article
  • Open access: Creative Commons BY-NC license
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    Modified nucleoside triphosphates exist in mammals

    H. Jiang, J. Xiong, F. Liu, C. Ma, X. Tang, B. Yuan and Y. Feng, Chem. Sci., 2018, Advance Article , DOI: 10.1039/C7SC05472F

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