Shapify: Paths to SARS-CoV-2 frameshifting pseudoknot.


Journal

PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922

Informations de publication

Date de publication:
02 2023
Historique:
received: 04 10 2022
accepted: 05 02 2023
revised: 10 03 2023
pubmed: 1 3 2023
medline: 15 3 2023
entrez: 28 2 2023
Statut: epublish

Résumé

Multiple coronaviruses including MERS-CoV causing Middle East Respiratory Syndrome, SARS-CoV causing SARS, and SARS-CoV-2 causing COVID-19, use a mechanism known as -1 programmed ribosomal frameshifting (-1 PRF) to replicate. SARS-CoV-2 possesses a unique RNA pseudoknotted structure that stimulates -1 PRF. Targeting -1 PRF in SARS-CoV-2 to impair viral replication can improve patients' prognoses. Crucial to developing these therapies is understanding the structure of the SARS-CoV-2 -1 PRF pseudoknot. Our goal is to expand knowledge of -1 PRF structural conformations. Following a structural alignment approach, we identify similarities in -1 PRF pseudoknots of SARS-CoV-2, SARS-CoV, and MERS-CoV. We provide in-depth analysis of the SARS-CoV-2 and MERS-CoV -1 PRF pseudoknots, including reference and noteworthy mutated sequences. To better understand the impact of mutations, we provide insight on -1 PRF pseudoknot sequence mutations and their effect on resulting structures. We introduce Shapify, a novel algorithm that given an RNA sequence incorporates structural reactivity (SHAPE) data and partial structure information to output an RNA secondary structure prediction within a biologically sound hierarchical folding approach. Shapify enhances our understanding of SARS-CoV-2 -1 PRF pseudoknot conformations by providing energetically favourable predictions that are relevant to structure-function and may correlate with -1 PRF efficiency. Applied to the SARS-CoV-2 -1 PRF pseudoknot, Shapify unveils previously unknown paths from initial stems to pseudoknotted structures. By contextualizing our work with available experimental data, our structure predictions motivate future RNA structure-function research and can aid 3-D modeling of pseudoknots.

Identifiants

pubmed: 36854032
doi: 10.1371/journal.pcbi.1010922
pii: PCOMPBIOL-D-22-01468
pmc: PMC10004594
doi:

Substances chimiques

RNA, Viral 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1010922

Informations de copyright

Copyright: © 2023 Trinity et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Luke Trinity (L)

Department of Computer Science, University of Victoria, Victoria, British Columbia, Canada.

Ian Wark (I)

Department of Computing Science, University of Alberta, Edmonton, Alberta, Canada.

Lance Lansing (L)

Department of Computer Science, University of Victoria, Victoria, British Columbia, Canada.

Hosna Jabbari (H)

Department of Computer Science, University of Victoria, Victoria, British Columbia, Canada.
Department of Computing Science, University of Alberta, Edmonton, Alberta, Canada.
Institute on Aging and Lifelong Health, Victoria, British Columbia, Canada.

Ulrike Stege (U)

Department of Computer Science, University of Victoria, Victoria, British Columbia, Canada.

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