1H, 13C and 15N chemical shift assignment of the stem-loop 5a from the 5′-UTR of SARS-CoV-2

Schnieders, Robbin; Peter, Stephen A.; Banijamali, Elnaz; Riad, Magdalena; Altincekic, Nadide; Bains, Jasleen Kaur; Ceylan, Betül; Fürtig, Boris; Grün, J. Tassilo; Hengesbach, Martin; Hohmann, Katharina F.; Hymon, Daniel; Knezic, Božana; Oxenfarth, Andreas; Petzold, Katja; Qureshi, Nusrat S.; Richter, Christian; Schlagnitweit, Judith; Schlundt, Andreas; Schwalbe, Harald; Stirnal, Elke; Sudakov, Alexey; Vögele, Jennifer; Wacker, Anna; Weigand, Julia E.; Wirmer‐Bartoschek, Julia; Wöhnert, Jens

doi:10.1007/s12104-021-10007-w

Cited by 7 publications

(12 citation statements)

References 41 publications

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“… 51 The low population of this state is not surprising, as the canonical UUCG tetraloop fold has been shown not to be stabilized to a sufficient degree within this force field. 52 While the detailed architecture of the hexaloop has not yet been solved experimentally, 11 , 32 our computational prediction and available NMR data cannot be easily reconciled in this case. We suggest that the simulations might be integrated with structural data collected in the future through a reweighting procedure.…”

Section: Resultsmentioning

confidence: 85%

“…Sugar pucker conformations for nucleotides 201 to 204 are predominantly in C2′-endo conformation, at variance with NMR data, which indicate C2′-endo conformations only at positions U202 and C203. 32 In one of the two simulations we observe the transient formation of a U200–U205 base-pair capped by a canonical UUCG tetraloop fold. 51 The low population of this state is not surprising, as the canonical UUCG tetraloop fold has been shown not to be stabilized to a sufficient degree within this force field.…”

Section: Resultsmentioning

confidence: 87%

“…Our predictions are overall compatible with NMR data, suggesting U194 to be base-paired and U195-G210 at least partially stable. 32 …”

Section: Resultsmentioning

confidence: 99%

“… 16 We then proceed by describing our predictions on four elements of increasing complexity ( Figure 1 ) and discuss the agreement with available NMR measurements. 32 , 33 Stem loop 5a (SL5a) is part of the four-way junction SL5 containing the AUG starting codon, whose function is linked to RNA packaging. 34 Stem loop 1 (SL1) has been suggested to play a role in escaping the viral mechanism inhibiting mRNA translation.…”

Section: Introductionmentioning

confidence: 99%

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Conformational Ensembles of Noncoding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations

2021

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The 5′ untranslated region (UTR) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome is a conserved, functional and structured genomic region consisting of several RNA stem-loop elements. While the secondary structure of such elements has been determined experimentally, their three-dimensional structures are not known yet. Here, we predict structure and dynamics of five RNA stem loops in the 5′-UTR of SARS-CoV-2 by extensive atomistic molecular dynamics simulations, more than 0.5 ms of aggregate simulation time, in combination with enhanced sampling techniques. We compare simulations with available experimental data, describe the resulting conformational ensembles, and identify the presence of specific structural rearrangements in apical and internal loops that may be functionally relevant. Our atomic-detailed structural predictions reveal a rich dynamics in these RNA molecules, could help the experimental characterization of these systems, and provide putative three-dimensional models for structure-based drug design studies.

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Section: Resultsmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 87%

“…Our predictions are overall compatible with NMR data, suggesting U194 to be base-paired and U195-G210 at least partially stable. 32 …”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Conformational Ensembles of Noncoding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations

2021

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“…1 ). Suggested by recent NMR studies, the 5′-UUCCGU-3′ sequence may adopt a conformation similar to 5′-UUCG-3′ tetra-loop ( Wacker et al 2020 ; Schnieders et al 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Structural phylogenetic analysis reveals lineage-specific RNA repetitive structural motifs in all coronaviruses and associated variations in SARS-CoV-2

Chen

Olsthoorn

2021

Virus Evolution

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In many single-stranded (ss) RNA viruses, the cis-acting packaging signal that confers selectivity genome packaging usually encompasses short structured RNA repeats. These structural units, termed repetitive structural motifs (RSMs), potentially mediate capsid assembly by specific RNA–protein interactions. However, general knowledge of the conservation and/or the diversity of RSMs in the positive-sense ssRNA coronaviruses (CoVs) is limited. By performing structural phylogenetic analysis, we identified a variety of RSMs in nearly all CoV genomic RNAs, which are exclusively located in the 5′-untranslated regions (UTRs) and/or in the inter-domain regions of poly-protein 1ab coding sequences in a lineage-specific manner. In all alpha- and beta-CoVs, except for Embecovirus spp, two to four copies of 5′-gUUYCGUc-3′ RSMs displaying conserved hexa-loop sequences were generally identified in Stem-loop 5 (SL5) located in the 5′-UTRs of genomic RNAs. In Embecovirus spp., however, two to eight copies of 5′-agc-3′/guAAu RSMs were found in the coding regions of non-structural protein (NSP) 3 and/or NSP15 in open reading frame (ORF) 1ab. In gamma- and delta-CoVs, other types of RSMs were found in several clustered structural elements in 5′-UTRs and/or ORF1ab. The identification of RSM-encompassing structural elements in all CoVs suggests that these RNA elements play fundamental roles in the life cycle of CoVs. In the recently emerged SARS-CoV-2, beta-CoV-specific RSMs are also found in its SL5, displaying two copies of 5′-gUUUCGUc-3′ motifs. However, multiple sequence alignment reveals that the majority of SARS-CoV-2 possesses a variant RSM harboring SL5b C241U, and intriguingly, several variations in the coding sequences of viral proteins, such as Nsp12 P323L, S protein D614G, and N protein R203K-G204R, are concurrently found with such variant RSM. In conclusion, the comprehensive exploration for RSMs reveals phylogenetic insights into the RNA structural elements in CoVs as a whole and provides a new perspective on variations currently found in SARS-CoV-2.

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1H, 13C and 15N assignment of stem-loop SL1 from the 5'-UTR of SARS-CoV-2

et al. 2021

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The stem-loop (SL1) is the 5'-terminal structural element within the single-stranded SARS-CoV-2 RNA genome. It is formed by nucleotides 7–33 and consists of two short helical segments interrupted by an asymmetric internal loop. This architecture is conserved among Betacoronaviruses. SL1 is present in genomic SARS-CoV-2 RNA as well as in all subgenomic mRNA species produced by the virus during replication, thus representing a ubiquitous cis-regulatory RNA with potential functions at all stages of the viral life cycle. We present here the 1H, 13C and 15N chemical shift assignment of the 29 nucleotides-RNA construct 5_SL1, which denotes the native 27mer SL1 stabilized by an additional terminal G-C base-pair.

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1H, 13C and 15N chemical shift assignment of the stem-loop 5a from the 5′-UTR of SARS-CoV-2

Cited by 7 publications

References 41 publications

Conformational Ensembles of Noncoding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations

Conformational Ensembles of Noncoding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations

Structural phylogenetic analysis reveals lineage-specific RNA repetitive structural motifs in all coronaviruses and associated variations in SARS-CoV-2

1H, 13C and 15N assignment of stem-loop SL1 from the 5'-UTR of SARS-CoV-2

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