4.7 Article

Dynamics of base pairs with low stability in RNA by solid-state nuclear magnetic resonance exchange spectroscopy

Journal

ISCIENCE
Volume 25, Issue 11, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.isci.2022.105322

Keywords

-

Funding

  1. National Key Research and Development Program of the Ministry of Science and Technology of the Peoples Republic of China [2016YFA0501203]
  2. National Natural Science Foundation of China [22274050, 21874004, 91953104]
  3. State Key Laboratory of Medicinal Chemical Biology [2020031]
  4. Fundamental Research Funds for the Central Universities
  5. Beijing National Laboratory for Molecular Sciences
  6. National High Magnetic Field Laboratory
  7. NSF [NSF/DMR-1644779]
  8. State of Florida

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Base pairs are essential units in RNA and their stability plays a crucial role in RNA functions. A solid-state NMR-based water-RNA exchange spectroscopy technique was developed to evaluate base pair stability. By applying this technique to a specific RNA complex, it was found that the U47.U51 base pair has low stability, indicating its involvement in the early stage of ligand release.
Base pairs are fundamental building blocks of RNA. The base pairs of low stability are often critical in RNA functions. Here, we develop a solid-state NMR-based water-RNA exchange spectroscopy (WaterREXSY) to characterize RNA in solid. The approach uses different chemical exchange rates between iminos and water to evaluate base pair stability; the less stable ones would exchange more frequently, leading to stronger cross-peaks on WaterREXSY. Applied to the riboA71-adenine complex (the 71nt-aptamer domain of add adenine riboswitch from Vibrio vulnificus), the U47.U51 base pair, which is critical in ligand binding, was found to be less stable than other base pairs. The imino-water exchange rates of U47 at different temperatures are about 500-800 s(-1 ), indeed indicative of low stability. This implies a highly complex and plastic triad involving U47.U51 and that the opening of the U47.U51 base pair may be the early stage of ligand release.

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