Review Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Ppublish 1 citation
PubMed: 36752040 DOI: 10.1093/bfgp/elac050
Experimental and computational methods for studying the dynamics of RNA-RNA interactions in SARS-COV2 genomes.
Brief Funct Genomics 23(1):46-54
Authors: Mansi Srivastava, Matthew R Dukeshire, Quoseena Mir, Okiemute Beatrice Omoru, Amirhossein Manzourolajdad, Sarath Chandra Janga
Affiliations
- Department of BioHealth Informatics, School of Informatics and Computing, Indiana University Purdue University, 535 West Michigan Street, Indianapolis, Indiana 46202, USA.
- Department of Biology, Indiana University, 1001 East 3rd St, Bloomington, Indiana 47405, USA.
- Department of Computer Science, Colgate University, Hamilton, NY, USA.
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Medical Research and Library Building, 975 West Walnut Street, Indianapolis, Indiana 46202, USA.
- Centre for Computational Biology and Bioinformatics, Indiana University School of Medicine, 5021 Health Information and Translational Sciences (HITS), 410 West 10th Street, Indianapolis, Indiana 46202, USA.
Abstract
Long-range ribonucleic acid (RNA)-RNA interactions (RRI) are prevalent in positive-strand RNA viruses, including Beta-coronaviruses, and these take part in regulatory roles, including the regulation of sub-genomic RNA production rates. Crosslinking of interacting RNAs and short read-based deep sequencing of resulting RNA-RNA hybrids have shown that these long-range structures exist in severe acute respiratory syndrome coronavirus (SARS-CoV)-2 on both genomic and sub-genomic levels and in dynamic topologies. Furthermore, co-evolution of coronaviruses with their hosts is navigated by genetic variations made possible by its large genome, high recombination frequency and a high mutation rate. SARS-CoV-2's mutations are known to occur spontaneously during replication, and thousands of aggregate mutations have been reported since the emergence of the virus. Although many long-range RRIs have been experimentally identified using high-throughput methods for the wild-type SARS-CoV-2 strain, evolutionary trajectory of these RRIs across variants, impact of mutations on RRIs and interaction of SARS-CoV-2 RNAs with the host have been largely open questions in the field. In this review, we summarize recent computational tools and experimental methods that have been enabling the mapping of RRIs in viral genomes, with a specific focus on SARS-CoV-2. We also present available informatics resources to navigate the RRI maps and shed light on the impact of mutations on the RRI space in viral genomes. Investigating the evolution of long-range RNA interactions and that of virus-host interactions can contribute to the understanding of new and emerging variants as well as aid in developing improved RNA therapeutics critical for combating future outbreaks.
MeSH
Coronavirus, Genomics, Genome, Viruses, Genome, Viral, Severe Acute Respiratory Syndrome-Related Coronavirus, Mutation, Rna