Evidence map›Paper›PMID 38842942›Full record

ArticleNucleic acids research2024

The 5'-terminal stem-loop RNA element of SARS-CoV-2 features highly dynamic structural elements that are sensitive to differences in cellular pH.

Sabrina Toews, Anna Wacker, Edgar M Faison, Elke Duchardt-Ferner, Christian Richter, Daniel Mathieu, Sandro Bottaro, Qi Zhang, Harald Schwalbe

Abstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

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  6. Biomolecular NMR assignments · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Sabrina ToewsInstitute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe-University Frankfurt, Frankfurt/Main, Hesse 60438, Germany.ORCID 0009-0008-5501-6276
Anna WackerInstitute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe-University Frankfurt, Frankfurt/Main, Hesse 60438, Germany.ORCID 0000-0001-5892-5661
Edgar M FaisonDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC27599, USA.ORCID 0000-0003-0207-767X
Elke Duchardt-FernerCenter for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-University Frankfurt, Frankfurt/Main, Hesse 60438, Germany.ORCID 0000-0001-7521-8264
Christian RichterInstitute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe-University Frankfurt, Frankfurt/Main, Hesse 60438, Germany.
Daniel MathieuBruker BioSpin GmbH, Ettlingen, Baden-Württemberg 76275, Germany.
Sandro BottaroLinderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark.ORCID 0000-0003-1606-890X
Qi ZhangDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC27599, USA.ORCID 0000-0003-1754-4058
Harald SchwalbeInstitute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe-University Frankfurt, Frankfurt/Main, Hesse 60438, Germany.ORCID 0000-0001-5693-7909

Funding

Bundesministerium für Wissenschaft und ForschungDeutsche Forschungsgemeinschaft 495006306Johann Wolfgang Goethe-University Frankfurtstate of Hesse
6 · The paper itself

Abstract

We present the nuclear magnetic resonance spectroscopy (NMR) solution structure of the 5'-terminal stem loop 5_SL1 (SL1) of the SARS-CoV-2 genome. SL1 contains two A-form helical elements and two regions with non-canonical structure, namely an apical pyrimidine-rich loop and an asymmetric internal loop with one and two nucleotides at the 5'- and 3'-terminal part of the sequence, respectively. The conformational ensemble representing the averaged solution structure of SL1 was validated using NMR residual dipolar coupling (RDC) and small-angle X-ray scattering (SAXS) data. We show that the internal loop is the major binding site for fragments of low molecular weight. This internal loop of SL1 can be stabilized by an A12-C28 interaction that promotes the transient formation of an A+•C base pair. As a consequence, the pKa of the internal loop adenosine A12 is shifted to 5.8, compared to a pKa of 3.63 of free adenosine. Furthermore, applying a recently developed pH-differential mutational profiling (PD-MaP) approach, we not only recapitulated our NMR findings of SL1 but also unveiled multiple sites potentially sensitive to pH across the 5'-UTR of SARS-CoV-2.

Indexed as

Nucleic Acid ConformationRNA, ViralSARS-CoV-25' Untranslated RegionsBase PairingBinding SitesCOVID-19Genome, ViralHumansHydrogen-Ion ConcentrationMagnetic Resonance SpectroscopyModels, MolecularScattering, Small AngleX-Ray Diffraction5' Untranslated RegionsRNA, Viral

Identifiers

PMID38842942
PMCPMC11260494

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.