Solid-state nanopore sensing reveals conformational changes induced by a mutation in a neuron-specific tRNAArg.

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$_{\mathrm{UCU}}^{\mathrm{Arg}}$, 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$^\

SUBMITTER: Dutt S 

PROVIDER: S-EPMC12834567 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature