Language
English
Publication Date
8-3-2026
Journal
Current Opinion in Structural Biology
DOI
10.1016/j.sbi.2026.103347
PMID
42546490
Abstract
RNA molecules populate complex structural landscapes that are continuously reshaped throughout the RNA lifecycle by equilibrium and non-equilibrium processes. Resolving these structural landscapes represents a central challenge in RNA biochemistry. We review recent advances in RNA chemical probing, sequencing, and computational deconvolution technologies that are revolutionizing our ability to measure the complexities of RNA folding in cells and the deep involvement of these complexities in RNA functional mechanisms. We highlight new methods for deconvolving structural ensembles, distinguishing isoform-specific architectures using long-read sequencing, capturing co-transcriptional folding intermediates in vivo, and measuring higher-order RNA structures while also underscoring remaining challenges. We conclude by outlining future directions in probe development, sequencing, and integrative modeling, and discuss how resolving RNA structural ensembles with increasingly high resolution will likely reveal new therapeutic opportunities to selectively target functional RNA heterogeneity.
Published Open-Access
yes
Recommended Citation
Anthony M Mustoe and Danny Incarnato, "Probing the Complexity of Cellular RNA Folding: Ensembles, Intermediates, and Isoforms" (2026). Faculty, Staff and Students Publications. 8187.
https://digitalcommons.library.tmc.edu/baylor_docs/8187