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Secondary structure determination of conserved SARS-CoV-2 RNA elements by NMR spectroscopy.
Nucleic Acids Res. 2020 12 16; 48(22):12415-12435.NA

Abstract

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.

Authors+Show Affiliations

Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Department of Biology, Technical University of Darmstadt, Schnittspahnstrasse 10, 64287 Darmstadt, Germany.Faculty of Chemistry, Weizmann Institute of Science, 7610001 Rehovot, Israel.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Department of Medical Biochemistry and Biophysics, Karolinska Institute, Biomedicum 9B, Solnavägen 9, 17177 Stockholm, Sweden.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.School of Medicine, Catholic University of Valencia, C/Quevedo 2, 46001 Valencia, Spain.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA.Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA.Institute for Molecular Biosciences.Institute for Molecular Biosciences.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Faculty of Chemistry, Weizmann Institute of Science, 7610001 Rehovot, Israel.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.School of Medicine, Catholic University of Valencia, C/Quevedo 2, 46001 Valencia, Spain.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Signals GmbH & Co. KG, Graf-von-Stauffenberg-Allee 83, 60438 Frankfurt/M, Germany.Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA.Signals GmbH & Co. KG, Graf-von-Stauffenberg-Allee 83, 60438 Frankfurt/M, Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Signals GmbH & Co. KG, Graf-von-Stauffenberg-Allee 83, 60438 Frankfurt/M, Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Molecular Biosciences.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute of Biophysical Chemistry, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University Frankfurt, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Department of Medical Biochemistry and Biophysics, Karolinska Institute, Biomedicum 9B, Solnavägen 9, 17177 Stockholm, Sweden.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Faculty of Chemistry, Weizmann Institute of Science, 7610001 Rehovot, Israel.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.School of Medicine, Catholic University of Valencia, C/Quevedo 2, 46001 Valencia, Spain.Department of Medical Biochemistry and Biophysics, Karolinska Institute, Biomedicum 9B, Solnavägen 9, 17177 Stockholm, Sweden.Department of Biology, Technical University of Darmstadt, Schnittspahnstrasse 10, 64287 Darmstadt, Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Department of Medical Biochemistry and Biophysics, Karolinska Institute, Biomedicum 9B, Solnavägen 9, 17177 Stockholm, Sweden.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Faculty of Chemistry, Weizmann Institute of Science, 7610001 Rehovot, Israel.Department of Medical Biochemistry and Biophysics, Karolinska Institute, Biomedicum 9B, Solnavägen 9, 17177 Stockholm, Sweden.Institute for Molecular Biosciences.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.School of Medicine, Catholic University of Valencia, C/Quevedo 2, 46001 Valencia, Spain.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Molecular Biosciences.Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA.Institute for Molecular Biosciences.Institute for Molecular Biosciences.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.Institute for Molecular Biosciences.Institute for Organic Chemistry and Chemical Biology, Max-von-Laue-Strasse 7, 60438 Frankfurt/M., Germany.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33167030

Citation

Wacker, Anna, et al. "Secondary Structure Determination of Conserved SARS-CoV-2 RNA Elements By NMR Spectroscopy." Nucleic Acids Research, vol. 48, no. 22, 2020, pp. 12415-12435.
Wacker A, Weigand JE, Akabayov SR, et al. Secondary structure determination of conserved SARS-CoV-2 RNA elements by NMR spectroscopy. Nucleic Acids Res. 2020;48(22):12415-12435.
Wacker, A., Weigand, J. E., Akabayov, S. R., Altincekic, N., Bains, J. K., Banijamali, E., Binas, O., Castillo-Martinez, J., Cetiner, E., Ceylan, B., Chiu, L. Y., Davila-Calderon, J., Dhamotharan, K., Duchardt-Ferner, E., Ferner, J., Frydman, L., Fürtig, B., Gallego, J., Grün, J. T., ... Zetzsche, H. (2020). Secondary structure determination of conserved SARS-CoV-2 RNA elements by NMR spectroscopy. Nucleic Acids Research, 48(22), 12415-12435. https://doi.org/10.1093/nar/gkaa1013
Wacker A, et al. Secondary Structure Determination of Conserved SARS-CoV-2 RNA Elements By NMR Spectroscopy. Nucleic Acids Res. 2020 12 16;48(22):12415-12435. PubMed PMID: 33167030.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Secondary structure determination of conserved SARS-CoV-2 RNA elements by NMR spectroscopy. AU - Wacker,Anna, AU - Weigand,Julia E, AU - Akabayov,Sabine R, AU - Altincekic,Nadide, AU - Bains,Jasleen Kaur, AU - Banijamali,Elnaz, AU - Binas,Oliver, AU - Castillo-Martinez,Jesus, AU - Cetiner,Erhan, AU - Ceylan,Betül, AU - Chiu,Liang-Yuan, AU - Davila-Calderon,Jesse, AU - Dhamotharan,Karthikeyan, AU - Duchardt-Ferner,Elke, AU - Ferner,Jan, AU - Frydman,Lucio, AU - Fürtig,Boris, AU - Gallego,José, AU - Grün,J Tassilo, AU - Hacker,Carolin, AU - Haddad,Christina, AU - Hähnke,Martin, AU - Hengesbach,Martin, AU - Hiller,Fabian, AU - Hohmann,Katharina F, AU - Hymon,Daniel, AU - de Jesus,Vanessa, AU - Jonker,Henry, AU - Keller,Heiko, AU - Knezic,Bozana, AU - Landgraf,Tom, AU - Löhr,Frank, AU - Luo,Le, AU - Mertinkus,Klara R, AU - Muhs,Christina, AU - Novakovic,Mihajlo, AU - Oxenfarth,Andreas, AU - Palomino-Schätzlein,Martina, AU - Petzold,Katja, AU - Peter,Stephen A, AU - Pyper,Dennis J, AU - Qureshi,Nusrat S, AU - Riad,Magdalena, AU - Richter,Christian, AU - Saxena,Krishna, AU - Schamber,Tatjana, AU - Scherf,Tali, AU - Schlagnitweit,Judith, AU - Schlundt,Andreas, AU - Schnieders,Robbin, AU - Schwalbe,Harald, AU - Simba-Lahuasi,Alvaro, AU - Sreeramulu,Sridhar, AU - Stirnal,Elke, AU - Sudakov,Alexey, AU - Tants,Jan-Niklas, AU - Tolbert,Blanton S, AU - Vögele,Jennifer, AU - Weiβ,Lena, AU - Wirmer-Bartoschek,Julia, AU - Wirtz Martin,Maria A, AU - Wöhnert,Jens, AU - Zetzsche,Heidi, PY - 2020/10/14/accepted PY - 2020/09/08/revised PY - 2020/06/23/received PY - 2020/11/10/pubmed PY - 2020/12/29/medline PY - 2020/11/9/entrez SP - 12415 EP - 12435 JF - Nucleic acids research JO - Nucleic Acids Res VL - 48 IS - 22 N2 - 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. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/33167030/Secondary_structure_determination_of_conserved_SARS_CoV_2_RNA_elements_by_NMR_spectroscopy_ L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkaa1013 DB - PRIME DP - Unbound Medicine ER -