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
  • 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].
PMID: 30202058 DOI: 10.1038/s41592-018-0121-0
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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