Detecting RNA base methylations in single cells by in situ hybridization.

Ranasinghe, Rohan T; Challand, Martin R; Ganzinger, Kristina A; Lewis, Benjamin W; Softley, Charlotte; Schmied, Wolfgang H; Horrocks, Mathew H; Shivji, Nadia et al. · Nat Commun · 2018

basic_science · Level V

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Abstract

Methylated bases in tRNA, rRNA and mRNA control a variety of cellular processes, including protein synthesis, antimicrobial resistance and gene expression. Currently, bulk methods that report the average methylation state of ~10<sup>4</sup>-10<sup>7</sup> cells are used to detect these modifications, obscuring potentially important biological information. Here, we use in situ hybridization of Molecular Beacons for single-cell detection of three methylations (m<sup>6</sup><sub>2</sub>A, m<sup>1</sup>G and m<sup>3</sup>U) that destabilize Watson-Crick base pairs. Our method-methylation-sensitive RNA fluorescence in situ hybridization-detects single methylations of rRNA, quantifies antibiotic-resistant bacteria in mixtures of cells and simultaneously detects multiple methylations using multicolor fluorescence imaging.

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