Duplex formation between the template and the nascent strand in the transcription-regulating sequences is associated with the site of template switching in SARS - CoV-2.
View / Open Files
Authors
D'Souza, Aaron R
Ingemarsdotter, Carin K
Jarvis, Isobel
Publication Date
2021-10-15Journal Title
RNA Biol
ISSN
1547-6286
Publisher
Informa UK Limited
Pages
1-9
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
D'Souza, A. R., Buckingham, A. B., Salasc, F., Ingemarsdotter, C. K., Iaconis, G., Jarvis, I., Groom, H. C., et al. (2021). Duplex formation between the template and the nascent strand in the transcription-regulating sequences is associated with the site of template switching in SARS - CoV-2.. RNA Biol, 1-9. https://doi.org/10.1080/15476286.2021.1975388
Description
Funder: Clinical Academic Reserve
Funder: NUS Department of Medicine
Funder: Biomedical Research Centre
Abstract
Recently published transcriptomic data of the SARS-CoV-2 coronavirus show that there is a large variation in the frequency and steady state levels of subgenomic mRNA sequences. This variation is derived from discontinuous subgenomic RNA synthesis, where the polymerase switches template from a 3' proximal genome body sequence to a 5' untranslated leader sequence. This leads to a fusion between the common 5' leader sequence and a 3' proximal body sequence in the RNA product. This process revolves around a common core sequence (CS) that is present at both the template sites that make up the fusion junction. Base-pairing between the leader CS and the nascent complementary minus strand body CS, and flanking regions (together called the transcription regulating sequence, TRS) is vital for this template switching event. However, various factors can influence the site of template switching within the same TRS duplex. Here, we model the duplexes formed between the leader and complementary body TRS regions, hypothesizing the role of the stability of the TRS duplex in determining the major sites of template switching for the most abundant mRNAs. We indicate that the stability of secondary structures and the speed of transcription play key roles in determining the probability of template switching in the production of subgenomic RNAs. We speculate on the effect of reported variant nucleotide substitutions on our models.
Keywords
RNA structure, TRS, Duplex, Template-switching, Sars-cov-2
Identifiers
PMC8459930, 34541994
External DOI: https://doi.org/10.1080/15476286.2021.1975388
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329744
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.