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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.

Published version
Peer-reviewed

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Type

Article

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Authors

D'Souza, Aaron R 
Buckingham, Amanda B  ORCID logo  https://orcid.org/0000-0001-7675-6320
Ingemarsdotter, Carin K 

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.

Description

Funder: Clinical Academic Reserve


Funder: NUS Department of Medicine


Funder: Biomedical Research Centre

Keywords

RNA structure, SARS-CoV-2, TRS, duplex, template-switching, Gene Expression Regulation, Viral, Mutation, Nucleic Acid Conformation, RNA Stability, RNA, Viral, SARS-CoV-2, Transcription, Genetic

Journal Title

RNA Biol

Conference Name

Journal ISSN

1547-6286
1555-8584

Volume Title

Publisher

Informa UK Limited