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Rational design of hairpin RNA excited states reveals multi-step transitions

Author

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  • Ge Han

    (Tsinghua University)

  • Yi Xue

    (Tsinghua University)

Abstract

RNA excited states represent a class of high-energy-level and thus low-populated conformational states of RNAs that are sequestered within the free energy landscape until being activated by cellular cues. In recent years, there has been growing interest in structural and functional studies of these transient states, but the rational design of excited states remains unexplored. Here we developed a method to design small hairpin RNAs with predefined excited states that exchange with ground states through base pair reshuffling, and verified these transient states by combining NMR relaxation dispersion technique and imino chemical shift prediction. Using van’t Hoff analysis and accelerated molecular dynamics simulations, a mechanism of multi-step sequential transition has been revealed. The efforts made in this study will expand the scope of RNA rational design, and also contribute towards improved predictions of RNA secondary structure.

Suggested Citation

  • Ge Han & Yi Xue, 2022. "Rational design of hairpin RNA excited states reveals multi-step transitions," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29194-8
    DOI: 10.1038/s41467-022-29194-8
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    1. Lorenzo Baronti & Ileana Guzzetti & Parisa Ebrahimi & Sarah Friebe Sandoz & Emilie Steiner & Judith Schlagnitweit & Bastian Fromm & Luis Silva & Carolina Fontana & Alan A. Chen & Katja Petzold, 2020. "Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA," Nature, Nature, vol. 583(7814), pages 139-144, July.
    2. Elizabeth A. Dethoff & Jeetender Chugh & Anthony M. Mustoe & Hashim M. Al-Hashimi, 2012. "Functional complexity and regulation through RNA dynamics," Nature, Nature, vol. 482(7385), pages 322-330, February.
    3. Yanjiao Wang & Ge Han & Xiuying Jiang & Tairan Yuwen & Yi Xue, 2021. "Chemical shift prediction of RNA imino groups: application toward characterizing RNA excited states," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    4. Evgenia N. Nikolova & Eunae Kim & Abigail A. Wise & Patrick J. O’Brien & Ioan Andricioaei & Hashim M. Al-Hashimi, 2011. "Transient Hoogsteen base pairs in canonical duplex DNA," Nature, Nature, vol. 470(7335), pages 498-502, February.
    5. William M. Dawson & Eric J. M. Lang & Guto G. Rhys & Kathryn L. Shelley & Christopher Williams & R. Leo Brady & Matthew P. Crump & Adrian J. Mulholland & Derek N. Woolfson, 2021. "Structural resolution of switchable states of a de novo peptide assembly," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    6. Satoshi Matsuura & Hiroki Ono & Shunsuke Kawasaki & Yi Kuang & Yoshihiko Fujita & Hirohide Saito, 2018. "Synthetic RNA-based logic computation in mammalian cells," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    7. Isaac J. Kimsey & Eric S. Szymanski & Walter J. Zahurancik & Anisha Shakya & Yi Xue & Chia-Chieh Chu & Bharathwaj Sathyamoorthy & Zucai Suo & Hashim M. Al-Hashimi, 2018. "Dynamic basis for dG•dT misincorporation via tautomerization and ionization," Nature, Nature, vol. 554(7691), pages 195-201, February.
    8. Elizabeth A. Dethoff & Katja Petzold & Jeetender Chugh & Anette Casiano-Negroni & Hashim M. Al-Hashimi, 2012. "Visualizing transient low-populated structures of RNA," Nature, Nature, vol. 491(7426), pages 724-728, November.
    9. Yi Xue & Brant Gracia & Daniel Herschlag & Rick Russell & Hashim M. Al-Hashimi, 2016. "Visualizing the formation of an RNA folding intermediate through a fast highly modular secondary structure switch," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    10. Marc Parisien & François Major, 2008. "The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data," Nature, Nature, vol. 452(7183), pages 51-55, March.
    11. Isaac J. Kimsey & Katja Petzold & Bharathwaj Sathyamoorthy & Zachary W. Stein & Hashim M. Al-Hashimi, 2015. "Visualizing transient Watson–Crick-like mispairs in DNA and RNA duplexes," Nature, Nature, vol. 519(7543), pages 315-320, March.
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