What is it about?
Ribosomal frameshifting is important for virus propagation. We use graph theory-based methods for representing RNA secondary structures of frameshifting elements in coronaviruses. By analyzing the topological changes over evolved coronavirus sequences for a range of lengths we explain alternative structural motifs of RNA frameshifting elements via key mutations from sequence evolution. This structural evolution helps interpret enhanced infectivity in SARS-CoV-2, the virus of Covid-19.
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Why is it important?
Frameshifting elements are highly conserved regions of coronaviruses that are responsible for programmed ribosomal frameshifting (PRF). Because PRF is key for viral infection and propagation, the frameshifting element (FSE) is an important anti-viral target. By revealing major conformational changes introduced by evolution as well as topology robustness by coevolution, we propose that topology changes contribute to tuning the frameshifting efficiency. Thus, our pinpointing key FSE locations involved in competing stems defines new potential therapeutic avenues. As proof of concept, we design minimal mutations that lead to dramatic conformational changes and result in decreased structural plasticity, which potentially enhance or diminish frameshifting. Our findings will provide insights in developing anti-viral therapeutics for a broad spectrum of coronaviruses.
Perspectives
I hope this article helps people understand how innovative research on RNA modeling contributes to the understanding of viruses and therapeutics development. Studying RNA structures via mathematical modeling helps understand RNA structural evolution. The design of minimal mutations via our graph-based inverse folding algorithm can serve as potential therapeutic avenues. Working on this study was a great pleasure as it applies RNA modeling to solve real-world problems of wide interest and importance!
Shuting Yan
New York University
Read the Original
This page is a summary of: Evolution of coronavirus frameshifting elements: Competing stem networks explain conservation and variability, Proceedings of the National Academy of Sciences, May 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2221324120.
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