Genome-scale deconvolution of RNA structure ensembles

Nat Methods. 2021 Mar;18(3):249-252. doi: 10.1038/s41592-021-01075-w. Epub 2021 Feb 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Algorithms*
  • COVID-19
  • Genome, Viral / genetics*
  • Humans
  • Mutation / drug effects
  • Mutation / genetics
  • Nucleic Acid Conformation*
  • RNA, Viral / chemistry*
  • RNA, Viral / genetics
  • SARS-CoV-2 / genetics*
  • Sulfuric Acid Esters / pharmacology

Substances

  • 3' Untranslated Regions
  • RNA, Viral
  • Sulfuric Acid Esters
  • dimethyl sulfate