4.8 Article

Genome-scale deconvolution of RNA structure ensembles

Journal

NATURE METHODS
Volume 18, Issue 3, Pages 249-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41592-021-01075-w

Keywords

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Funding

  1. Dutch Research Council (Netherlands Organisation for Scientific Research, NWO) as part of the research programme NWO Open Competitie ENW-XS [OCENW.XS3.044]
  2. Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen
  3. Associazione Italiana per la Ricerca sul Cancro (AIRC), grant AIRC IG 2017 [20240]
  4. Leiden University Fund (LUF)
  5. Bontius Foundation
  6. Associazione Italiana per la Ricerca sul Cancro (AIRC), PRIN 2017

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RNA structure heterogeneity poses a significant challenge in chemical probing, but the introduction of the DRACO algorithm allows for the deconvolution of coexisting RNA conformations. Analysis of the SARS-CoV-2 genome using DMS-MaPseq and DRACO reveals multiple regions with two mutually exclusive conformations, shedding light on the heterogeneity of the RNA structurome.
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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