Effects of Noncanonical Base Pairing on RNA Folding: Structural Context and Spatial Arrangements of G·A Pairs

Noncanonical base pairs play important roles in assembling the three-dimensional structures critical to the diverse functions of RNA. These associations contribute to the looped segments that intersperse the canonical double-helical elements within folded, globular RNA molecules. They stitch together various structural elements, serve as recognition elements for other molecules, and act as sites of intrinsic stiffness or deformability. This work takes advantage of new software (DSSR) designed to streamline the analysis and annotation of RNA three-dimensional structures. The multiscale structural information gathered for individual molecules, combined with the growing number of unique, well-resolved RNA structures, makes it possible to examine the collective features deeply and to uncover previously unrecognized patterns of chain organization. Here we focus on a subset of noncanonical base pairs involving guanine and adenine and the links between their modes of association, secondary structural context, and contributions to tertiary folding. The rigorous descriptions of base-pair geometry that we employ facilitate characterization of recurrent geometric motifs and the structural settings in which these arrangements occur. Moreover, the numerical parameters hint at the natural motions of the interacting bases and the pathways likely to connect different spatial forms. We draw attention to higher-order multiplexes involving two or more G·A pairs and the roles these associations appear to play in bridging different secondary structural units. The collective data reveal pairing propensities in base organization, secondary structural context, and deformability and serve as a starting point for further multiscale investigations and/or simulations of RNA folding.

非经典碱基对（Noncanonical base pairs）在组装RNA多样功能所依赖的三维结构中发挥关键作用。这类碱基配对参与形成环状区段，这些区段穿插于折叠为球状的RNA分子内的经典双螺旋结构单元之间。它们可将各类结构单元连接整合，作为其他分子的识别位点，并充当固有刚性或可变形性的作用位点。本研究借助专为优化RNA三维结构分析与注释而开发的新型软件DSSR。针对单个RNA分子采集的多尺度结构信息，结合日益增多的独特且高解析度的RNA结构数据，使得我们能够深入探究集体结构特征，并发掘此前未被认知的链组织模式。本研究聚焦于一类涉及鸟嘌呤（guanine）与腺嘌呤（adenine）的非经典碱基对子集，并探讨其配对模式、二级结构环境以及对三级折叠的贡献之间的关联。我们所采用的碱基对几何构型严谨表征方法，有助于识别反复出现的几何基序以及这类排列所存在的结构环境。此外，相关数值参数能够揭示相互作用碱基的自然运动特性，以及连接不同空间构象的潜在路径。我们着重关注包含两对及以上G·A配对的高阶复合结构，并探讨这类配对在连接不同二级结构单元中所发挥的作用。本次汇总的数据揭示了碱基组织、二级结构环境以及可变形性中的配对偏好性，同时可为后续开展RNA折叠的多尺度研究及/或模拟提供基础起点。