Untangling the pseudoknots of SARS-CoV-2: Insights into structural heterogeneity and plasticity

Justin Aruda; Scott L Grote; Silvi Rouskin

doi:10.1016/j.sbi.2024.102912

Untangling the pseudoknots of SARS-CoV-2: Insights into structural heterogeneity and plasticity

Curr Opin Struct Biol. 2024 Oct:88:102912. doi: 10.1016/j.sbi.2024.102912. Epub 2024 Aug 21.

Authors

Justin Aruda¹, Scott L Grote², Silvi Rouskin³

Affiliations

¹ Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Harvard Program in Biological and Biomedical Sciences, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA.
² Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
³ Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: silvi@hms.harvard.edu.

PMID: 39168046
DOI: 10.1016/j.sbi.2024.102912

Abstract

Since the onset of the COVID-19 pandemic, one productive area of research has focused on the intricate two- and three-dimensional structures taken on by SARS-CoV-2's RNA genome. These structures control essential viral processes, making them tempting targets for therapeutic intervention. This review focuses on two such structured regions, the frameshift stimulation element (FSE), which controls the translation of viral protein, and the 3' untranslated region (3' UTR), which is thought to regulate genome replication. For the FSE, we discuss its canonical pseudoknot's threaded and unthreaded topologies, as well as the diversity of competing two-dimensional structures formed by local and long-distance base pairing. For the 3' UTR, we review the evidence both for and against the formation of its replication-enabling pseudoknot.

Publication types

Review

MeSH terms

3' Untranslated Regions*
COVID-19 / virology
Genome, Viral
Humans
Nucleic Acid Conformation*
RNA, Viral* / chemistry
RNA, Viral* / genetics
RNA, Viral* / metabolism
SARS-CoV-2* / chemistry
SARS-CoV-2* / genetics

Substances

RNA, Viral
3' Untranslated Regions