Jang Sukjin S, Ray Korak Kumar, Lynall David G, Shepard Kenneth L, Nuckolls Colin, Gonzalez Ruben L
Department of Chemistry, Columbia University, NY, NY 10027, United States.
Department of Electrical Engineering, Columbia University, NY, NY 10027, United States.
Nucleic Acids Res. 2025 Jul 19;53(14). doi: 10.1093/nar/gkaf681.
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.
最近的研究表明，像RNA这样的生物聚合物在多种折叠结构之间相互转换的机制对其细胞功能至关重要。阐明这些机制的一个主要障碍是缺乏能够解析功能相关生物分子结构之间这些相互转换的实验方法。在这里，我们使用具有微秒时间分辨率的纳米电子器件，在单分子水平上剖析了超稳定RNA（UUCG茎环）执行的全套结构重排。我们表明，茎环沿着两条折叠途径采样至少四种构象，导致两种不同的折叠结构，其中只有一种以前被观察到。通过调节其柔韧性，茎环可以在这些途径之间进行自适应选择，使其既能快速折叠又能抵抗解折叠。这种通过柔韧性的补偿性变化实现稳定的机制拓宽了我们对稳定RNA结构的理解，我们预计它将作为一种所有生物聚合物都可采用的通用策略。
