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

Wacker A, Weigand JE, Akabayov SR, Altincekic N, Bains JK, Banijamali E, Binas O, Castillo-Martinez J, Cetiner E, Ceylan B, Chiu LY, Davila-Calderon J, Dhamotharan K, Duchardt-Ferner E, Ferner J, Frydman L, Fürtig B, Gallego J, Grün JT, Hacker C, Haddad C, Hähnke M, Hengesbach M, Hiller F, Hohmann KF, Hymon D, de Jesus V, Jonker H, Keller H, Knezic B, Landgraf T, Löhr F, Luo L, Mertinkus KR, Muhs C, Novakovic M, Oxenfarth A, Palomino-Schätzlein M, Petzold K, Peter SA, Pyper DJ, Qureshi NS, Riad M, Richter C, Saxena K, Schamber T, Scherf T, Schlagnitweit J, Schlundt A, Schnieders R, Schwalbe H, Simba-Lahuasi A, Sreeramulu S, Stirnal E, Sudakov A, Tants JN, Tolbert BS, Vögele J, Weiß L, Wirmer-Bartoschek J, Wirtz Martin MA, Wöhnert J, Zetzsche H

Nucleic Acids Res 48 (22) 12415-12435 [2020-11-10; online 2020-11-10]

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.

Category: Biochemistry

Category: Other

Type: Journal article

PubMed 33167030

DOI 10.1093/nar/gkaa1013

Crossref 10.1093/nar/gkaa1013

pii: 5961789
COVID19-NMR project: Experimental data
NA: Nuclear magnetic resonance (NMR) spectroscopy deposited in See Table 1 of the article for accession numbers.

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