1. Academic Validation
  2. COMRADES determines in vivo RNA structures and interactions

COMRADES determines in vivo RNA structures and interactions

  • Nat Methods. 2018 Oct;15(10):785-788. doi: 10.1038/s41592-018-0121-0.
Omer Ziv 1 2 Marta M Gabryelska 3 Aaron T L Lun 4 Luca F R Gebert 5 Jessica Sheu-Gruttadauria 5 Luke W Meredith 6 Zhong-Yu Liu 7 8 Chun Kit Kwok 9 Cheng-Feng Qin 7 Ian J MacRae 5 Ian Goodfellow 6 John C Marioni 4 10 11 Grzegorz Kudla 12 Eric A Miska 13 14 15
Affiliations

Affiliations

  • 1 Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK. [email protected].
  • 2 Department of Genetics, University of Cambridge, Cambridge, UK. [email protected].
  • 3 MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland, UK.
  • 4 Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • 5 Department of Integrative Structural and Computational Biology, the Scripps Research Institute, La Jolla, CA, USA.
  • 6 Department of Pathology, University of Cambridge, Cambridge, UK.
  • 7 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
  • 8 School of Medicine (Shenzhen), Sun Yat-sen University, Guangzhou, China.
  • 9 Department of Chemistry, City University of Hong Kong, Hong Kong, China.
  • 10 European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK.
  • 11 Wellcome Sanger Institute, Cambridge, UK.
  • 12 MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland, UK. [email protected].
  • 13 Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK. [email protected].
  • 14 Department of Genetics, University of Cambridge, Cambridge, UK. [email protected].
  • 15 Wellcome Sanger Institute, Cambridge, UK. [email protected].
Abstract

The structural flexibility of RNA underlies fundamental biological processes, but there are no methods for exploring the multiple conformations adopted by RNAs in vivo. We developed cross-linking of matched RNAs and deep sequencing (COMRADES) for in-depth RNA conformation capture, and a pipeline for the retrieval of RNA structural ensembles. Using COMRADES, we determined the architecture of the Zika virus RNA genome inside cells, and identified multiple site-specific interactions with human noncoding RNAs.

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