Issue 3, 2024

Reversible oxidative dimerization of 4-thiouridines in tRNA isolates

Abstract

The occurrence of non-canonical nucleoside structures in RNA of biological or synthetic origin has encountered several recent boosts in attention, namely in the context of RNA modifications, and with an eye to RNA vaccines. New nucleoside structures introduce added functionality and function into biopolymers that are otherwise rather homogenous in their chemical structure. Here, we report the discovery of a presumed RNA modification that was identified by combination of liquid chromatography–tandem mass spectrometry (LC–MS/MS) with stable isotope labelling as a dimer of the known RNA modification 4-thiouridine (s4U). The disulfide-linked structure, which had previously been synthetically introduced into RNA, was here formed spontaneously in isolates of E. coli tRNA. Judicious application of stable isotope labelling suggested that this presumed new RNA modification was rather generated ex vivo by oxidation with ambient oxygen. These findings do not only underscore the need for caution in the discovery of new RNA modifications with respect to artifacts, but also raise awareness of an RNA vulnerability, especially to oxidative damage, during its transport or storage.

Graphical abstract: Reversible oxidative dimerization of 4-thiouridines in tRNA isolates

Supplementary files

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Article information

Article type
Paper
Submitted
09 nov. 2023
Accepted
31 ene. 2024
First published
01 feb. 2024
This article is Open Access
Creative Commons BY license

RSC Chem. Biol., 2024,5, 216-224

Reversible oxidative dimerization of 4-thiouridines in tRNA isolates

L. Bessler, J. Groß, C. J. Kampf, T. Opatz and M. Helm, RSC Chem. Biol., 2024, 5, 216 DOI: 10.1039/D3CB00221G

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