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Secondary structure determination of conserved SARS-CoV-2 RNA elements by NMR spectroscopy

  • The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5′ end, the ribosomal frameshift segment and the 3′-untranslated region (3′-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.

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Author:Anna WackerORCiDGND, Julia WeigandORCiDGND, Sabine R. AkabayovORCiD, Nadide AltınçekiçORCiDGND, Jasleen Kaur BainsORCiDGND, Elnaz Banijamali, Oliver BinasORCiDGND, Jesus Castillo-Martinez, Erhan Can ÇetinerORCiDGND, Betül Ceylan, Liang-Yuan ChiuORCiD, Jesse Davila-CalderonORCiD, Karthikeyan DhamotharanORCiDGND, Elke Duchardt-FernerORCiD, Jan FernerORCiDGND, Lucio FrydmanORCiD, Boris FürtigORCiDGND, José GallegoORCiD, J. Tassilo GrünORCiDGND, Carolin HackerORCiDGND, Christina Haddad, Martin Jens HähnkeGND, Martin HengesbachORCiDGND, Fabian Hiller, Katharina Felicitas HohmannGND, Daniel Hymon, Vanessa de Jesus, Henry Jonker, Heiko KellerGND, Božana KnežićGND, Tom LandgrafORCiDGND, Frank LöhrORCiD, Le Luo, Klara Rebecca MertinkusORCiD, Christina Muhs, Mihajlo Novakovic, Andreas Oxenfarth, Martina Palomino-SchätzleinORCiD, Katja PetzoldORCiD, Stephen PeterGND, Dennis Joshua Pyper, Nusrat QureshiORCiDGND, Magdalena RiadORCiD, Christian RichterORCiDGND, Krishna SaxenaORCiDGND, Tatjana SchamberORCiD, Tali ScherfORCiD, Judith Schlagnitweit, Andreas SchlundtORCiDGND, Robbin SchniedersGND, Harald SchwalbeORCiDGND, Alvaro Simba-Lahuasi, Sridhar SreeramuluORCiDGND, Elke Stirnal, Alexey Sudakov, Jan-Niklas TantsORCiD, Blanton S. TolbertORCiD, Jennifer VögeleORCiD, Lena WeißORCiD, Julia Wirmer-BartoschekORCiD, Maria Alexandra Wirtz MartinORCiD, Jens WöhnertORCiDGND, Heidi ZetzscheORCiDGND
URN:urn:nbn:de:hebis:30:3-633055
DOI:https://doi.org/10.1093/nar/gkaa1013
ISSN:1362-4962
Parent Title (English):Nucleic acids research
Publisher:Oxford Univ. Press
Place of publication:Oxford
Document Type:Article
Language:English
Date of Publication (online):2020/11/10
Date of first Publication:2020/11/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/10/19
Volume:48
Issue:22
Page Number:21
First Page:12415
Last Page:12435
Note:
Funding: Goethe University; Deutsche Forschungsgemeinschaft (DFG) [CRC902]; National Institutes of Health [U54AI50470, R01GM126833 B.S.T.]; EU Horizon 2020 [828946]; Weizmann's Internal Coronavirus Fund; German-Israel Foundation [G-1501-302]; Spanish Ministerio de Economía y Competitividad [RTI2018-093935-B-I00]; la Caixa Banking Foundation; Catholic University of Valencia; Hessisches Ministerium für Wissenschaft und Kunst [BMRZ]; iNEXT-Discovery [871037]. Funding for open access charge: DFG.
Note:
This paper is linked to: doi:10.1093/nar/gkaa1053
Note:
Chemical shifts are deposited at BMRB. All experimental data are deposited and can be downloaded at http://covid19-nmr.de.
HeBIS-PPN:505145650
Institutes:Biochemie, Chemie und Pharmazie
Biowissenschaften
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (English):License LogoCreative Commons - Namensnennung-Nicht kommerziell 4.0