Genome-scale deconvolution of RNA structure ensembles.

Morandi, Edoardo; Manfredonia, Ilaria; Simon, Lisa M; Anselmi, Francesca; van Hemert, Martijn J; Oliviero, Salvatore; Incarnato, Danny · Nat Methods · 2021

basic_science · Level V

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Abstract

RNA structure heterogeneity is a major challenge when querying RNA structures with chemical probing. We introduce DRACO, an algorithm for the deconvolution of coexisting RNA conformations from mutational profiling experiments. Analysis of the SARS-CoV-2 genome using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and DRACO, identifies multiple regions that fold into two mutually exclusive conformations, including a conserved structural switch in the 3' untranslated region. This work may open the way to dissecting the heterogeneity of the RNA structurome.

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