Genome-scale deconvolution of RNA structure ensembles

Nature Methods, vol. 18, pp. 249–252

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. The DRACO algorithm deconvolutes coexisting RNA structures from mutational profiling experiments, and can be applied to bacterial regulatory structures and elements from the SARS-CoV-2 genome.

Authors 6

1. Edoardo Morandi

   University of Groningen · University of Turin

   Affiliation as printed

   Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, the Netherlands

   Dipartimento di Scienze della Vita e Biologia dei Sistemi, Università di Torino, Torino, Italy

2. Ilaria Manfredonia

   University of Groningen

   Affiliation as printed

   Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, the Netherlands

3. Lisa Marie Simon

   University of Turin

   Affiliation as printed

   Dipartimento di Scienze della Vita e Biologia dei Sistemi, Università di Torino, Torino, Italy

4. Martijn J. van Hemert Aachen Department of Medical Microbiology Molecular Virology Laboratory

   Leiden University Medical Center

   Affiliation as printed

   Department of Medical Microbiology, Molecular Virology Laboratory, Leiden University Medical Center, Leiden, the Netherlands

5. Salvatore Oliviero corresponding

   Italian institute for Genomic Medicine · University of Turin

   Affiliation as printed

   Dipartimento di Scienze della Vita e Biologia dei Sistemi, Università di Torino, Torino, Italy. salvatore.oliviero@unito.it

   Italian Institute for Genomic Medicine (IIGM), Candiolo, Italy. salvatore.oliviero@unito.it

   Dipartimento di Scienze della Vita e Biologia dei Sistemi, Università di Torino, Torino, Italy

6. Danny Incarnato corresponding

   University of Groningen

   Affiliation as printed

   Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, the Netherlands. d.incarnato@rug.nl

   Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, the Netherlands