Highly conserved s2m element of SARS-CoV-2 dimerizes via a kissing complex and interacts with host miRNA-1307-3p

Published

December 1, 2021

Author(s)

Joshua A. Imperatore, Caylee L. Cunningham, Kendy A. Pellegrene, Robert Brinson, John Marino, Jeffery D. Evanseck, Mihaela R. Mihailescu

Abstract

The ongoing COVID-19 pandemic highlights the necessity for a more fundamental understanding of the coronavirus life cycle. The causative agent of the disease, SARS-CoV-2, is being studied extensively from a structural standpoint in order to gain insight into key molecular mechanisms required for its survival. Contained within the untranslated regions of the SARS-CoV-2 genome are various conserved stemloop elements that are believed to function in RNA replication, viral protein translation, and discontinuous transcription. While the majority of these regions are variable in sequence, a 41-nucleotide s2m element within the genome 3 untranslated region is highly conserved among coronaviruses and three other viral families. In this study, we demonstrate that the SARS-CoV-2 s2m element dimerizes by forming an intermediate homodimeric kissing complex structure that is subsequently converted to a hermodynamically stable duplex conformation. This process is aided by the viral nucleocapsid protein, potentially indicating a role in mediating genome dimerization. Furthermore, we demonstrate that the s2m element interacts with multiple copies of host cellular microRNA (miRNA) 1307-3p. Taken together, our results highlight the potential significance of the dimer structures formed by the s2m element in key biological processes and implicate the motif as a possible therapeutic drug target for COVID-19 and other coronavirus-related diseases.

Citation

Nucleic Acids Research

Volume

50

Issue

2

Pub Type

Journals

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DOI Link

Keywords

SARS-CoV-2, RNA, genome dimerization, miRNA

Citation

Imperatore, J. , Cunningham, C. , Pellegrene, K. , Brinson, R. , Marino, J. , Evanseck, J. and Mihailescu, M. (2021), Highly conserved s2m element of SARS-CoV-2 dimerizes via a kissing complex and interacts with host miRNA-1307-3p, Nucleic Acids Research, [online], https://doi.org/10.1093/nar/gkab1226 (Accessed April 25, 2024)