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| Title | Solid-state nanopore sensing reveals conformational changes induced by a mutation in a neuron-specific tRNAArg. |
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| Journal, issue, pages | Nucleic Acids Res, Vol. 54, Issue 2, Year 2026 |
| Publish date | Jan 14, 2026 |
 Authors | Shankar Dutt / Lien B Lai / Rahul Mehta / Buddini I Karawdeniya / Y M Nuwan D Y Bandara / Andrew J Clulow / Sebastian Glatt / Venkat Gopalan / Patrick Kluth /     |
| PubMed Abstract | We demonstrate that solid-state nanopore sensing is a powerful single-molecule method for analyzing RNA conformational ensembles. As a model, we employed n-Tr20, a neuron-specific cytoplasmic tRNA$_ ...We demonstrate that solid-state nanopore sensing is a powerful single-molecule method for analyzing RNA conformational ensembles. As a model, we employed n-Tr20, a neuron-specific cytoplasmic tRNA$_{\mathrm{UCU}}^{\mathrm{Arg}}$, whose C50U mutation is associated with neurodegeneration in C57BL/6J mice. Maturation of the n-Tr20$^{\mathrm{C50U}}$ precursor is impaired as the mutation stabilizes a conformational ensemble different from the wild type. To gain insights into how this mutation engenders structural differences, we used solid-state nanopore sensing for the real-time identification of metastable conformers that are not easily observable by ensemble methods. Ion-current traces recorded using an 8 nm nanopore revealed broad contours of the conformational landscape of n-Tr20/n-Tr20$^\mathrm{C50U}$ $\pm$ Mg$^{2+}$. Additionally, cryo-electron microscopy analysis and small-angle X-ray scattering studies revealed structural plasticity consistent with the nanopore-sensing data. Since dynamics undergird RNA (dys)function in cellular physiology and pathology, nanopore sensing to determine RNA conformational sampling is a valuable addition to the growing RNA structural analysis toolkit. |
 External links | Nucleic Acids Res / PubMed:41587754 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 9.6 - 9.9 Å |
| Structure data |  EMDB-55720: Cryo-EM reconstruction for n-Tr20U.  EMDB-55721: Cryo-EM structure of nTr20 tRNA |
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Homo sapiens (human)