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Updated: Jul 21, 2025

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
Published on: December 9, 2022
A novel approach to finding conserved features in low-variability gene alignments characterises RNA motifs in
Jordan P Skittrall1, Nerea Irigoyen2, Ian Brierley2
1Department of Pathology, Division of Virology, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge, CB2 0QQ, UK. jps55@cam.ac.uk.
Abstract:
Collections of genetic sequences belonging to related organisms contain information on the evolutionary constraints to which the organisms have been subjected. Heavily constrained regions can be investigated to understand their roles in an organism's life cycle, and drugs can be sought to disrupt these roles. In organisms with low genetic diversity, such as newly-emerged pathogens, it is key to obtain this information early to develop new treatments. Here, we present methods that ensure we can leverage all the information available in a low-signal, low-noise set of sequences, to find contiguous regions of relatively conserved nucleic acid. We demonstrate the application of these methods by analysing over 5 million genome sequences of the recently-emerged RNA virus SARS-CoV-2 and correlating these results with an analysis of 119 genome sequences of SARS-CoV. We propose the precise location of a previously described packaging signal, and discuss explanations for other regions of high conservation.
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