COMRADES determines in vivo RNA structures and interactions.


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Authors
Gabryelska, Marta M 
Gebert, Luca FR 
Sheu-Gruttadauria, Jessica 
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.

Description
Keywords
High-Throughput Nucleotide Sequencing, Humans, Nucleic Acid Conformation, RNA, Viral, RNA-Binding Proteins, Sequence Analysis, RNA, Transcriptome, Zika Virus, Zika Virus Infection
Journal Title
Nat Methods
Conference Name
Journal ISSN
1548-7091
1548-7105
Volume Title
15
Publisher
Springer Science and Business Media LLC
Sponsorship
Cancer Research UK (18583)
Wellcome Trust (104640/Z/14/Z)
Wellcome Trust (092096/Z/10/Z)
Wellcome Trust (207498/Z/17/Z)
Wellcome Trust (207498/Z/17/Z)
Cancer Research Uk (None)
This work was supported by Cancer Research UK (C13474/A18583, C6946/A14492) and the Wellcome Trust (104640/Z/14/Z, 092096/Z/10/Z) to E.A.M. O.Z. was supported by the Human Frontier Science Program (HFSP, LT000558/2015), the European Molecular Biology Organization (EMBO, ALTF1622-2014), and the Blavatnik Family Foundation postdoctoral fellowship. G.K. and M.G. were supported by Wellcome Trust grant 207507 and UK Medical Research Council. A.T.L.L. and J.C.M. were supported by core funding from Cancer Research UK (award no. 17197 to JCM). J.C.M was also supported by core funding from EMBL. I.G. and L.W.M. were supported by the Wellcome Trust Senior Fellowship in Basic Biomedical Science to I.G. (207498/Z/17/Z). I.J.M., L.F.G. and J.S.-G. were supported by grants R01GM104475 and R01GM115649 from NIGMS. C.K.K was supported by City University of Hong Kong Projects 9610363 and 7200520, Croucher Foundation Project 9500030 and Hong Kong RGC Projects 9048103 and 9054020. C.-F.Q. was supported by the NSFC Excellent Young Scientist Fund 81522025 and the Newton Advanced Fellowship from the Academy of Medical Sciences, UK.