Conformational dynamics of the frameshift stimulatory structure in HIV-1

RNA
Dustin B RitchieMichael T Woodside

Abstract

Programmed ribosomal frameshifting (PRF) in HIV-1 is thought to be stimulated by a hairpin in the mRNA, although a pseudoknot-like triplex has also been proposed. Because the conformational dynamics of the stimulatory structure under tension applied by the ribosomal helicase during translation may play an important role in PRF, we used optical tweezers to apply tension to the HIV stimulatory structure and monitor its unfolding and refolding dynamics. The folding and unfolding kinetics and energy landscape of the hairpin were measured by ramping the force on the hairpin up and down, providing a detailed biophysical characterization. Unexpectedly, whereas unfolding reflected the simple two-state behavior typical of many hairpins, refolding was more complex, displaying significant heterogeneity. Evidence was found for multiple refolding pathways as well as previously unsuspected, partially folded intermediates. Measuring a variant mRNA containing only the sequence required to form the proposed triplex, it behaved largely in the same way. Nonetheless, very rarely, high-force unfolding events characteristic of pseudoknot-like structures were observed. The rare occurrence of the triplex suggests that the hairpin is the functional sti...Continue Reading

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Citations

Apr 4, 2018·Cold Spring Harbor Perspectives in Biology·Thomas E DeverRachel Green
Aug 15, 2019·Proceedings of the National Academy of Sciences of the United States of America·Matthew T J HalmaMichael T Woodside
Jun 18, 2020·Nature Communications·Martin MiklEran Segal
Dec 20, 2018·Nucleic Acids Research·Ann MukhortavaMichael Schlierf
Jan 20, 2021·PLoS Computational Biology·Sara Ibrahim OmarMichael T Woodside
Jul 15, 2021·Computational and Structural Biotechnology Journal·Kai-Chun Chang, Jin-Der Wen
Aug 8, 2021·Nature Communications·Krishna NeupaneMichael T Woodside
Jan 14, 2020·The Journal of Physical Chemistry Letters·Frederico Campos Freitas, Ronaldo Junio de Oliveira
Aug 28, 2021·International Journal of Molecular Sciences·Anna Wypijewska Del NogalL Marcus Wilhelmsson

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