2025/07/14 by Sukjin S Jang, Korak Kumar Ray, David Lynall +3 · 1 voice · 2 citations
Biochemistry, Genetics and Molecular Biology · #Biological system #Biology #Biophysics #Computational biology #Flexibility (engineering) #Folding (DSP implementation) #Genetics #RNA #RNA Research and Splicing #RNA and protein synthesis mechanisms #RNA modifications and cancer #Stem-loop
paper · pdf · doi:10.1093/nar/gkaf681
openalex publication_date 2025/07/14 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Recent studies have demonstrated that the mechanisms through which biopolymers like RNA interconvert between multiple folded structures are critical for their cellular functions. A major obstacle to elucidating these mechanisms is the lack of experimental approaches that can resolve these interconversions between functionally relevant biomolecular structures. Here, we dissect the complete set of structural rearrangements executed by an ultra-stable RNA, the UUCG stem-loop, at the single-molecule level using a nano-electronic device with microsecond time resolution. We show that the stem-loop samples at least four conformations along two folding pathways leading to two distinct folded structures, only one of which has been previously observed. By modulating its flexibility, the stem-loop can adaptively select between these pathways, enabling it to both fold rapidly and resist unfolding. This mechanism of stabilization through compensatory changes in flexibility broadens our understanding of stable RNA structures and we expect it to serve as a general strategy that can be employed by all biopolymers.