International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland.
Nucleic Acids Res. 2024 Oct 14;52(18):10850-10861. doi: 10.1093/nar/gkae758.
Non-coding RNAs play a major role in diverse processes in living cells with their sequence and spatial structure serving as the principal determinants of their function. Superposition of RNA 3D structures is the most accurate method for comparative analysis of RNA molecules and for inferring structure-based sequence alignments. Topology-independent superposition is particularly relevant, as evidenced by structurally similar RNAs with sequence permutations such as tRNA and Y RNA. To date, state-of-the-art methods for RNA 3D structure superposition rely on intricate heuristics, and the potential for topology-independent superposition has not been exhausted. Recently, we introduced the ARTEM method for unrestrained pairwise superposition of RNA 3D modules and now we developed it further to solve the global RNA 3D structure alignment problem. Our new tool ARTEMIS significantly outperforms state-of-the-art tools in both sequentially-ordered and topology-independent RNA 3D structure superposition. Using ARTEMIS we discovered a helical packing motif to be preserved within different backbone topology contexts across various non-coding RNAs, including multiple ribozymes and riboswitches. We anticipate that ARTEMIS will be essential for elucidating the landscape of RNA 3D folds and motifs featuring sequence permutations that thus far remained unexplored due to limitations in previous computational approaches.
非编码 RNA 以其序列和空间结构作为功能的主要决定因素，在活细胞的各种过程中发挥着重要作用。RNA 三维结构的叠加是比较分析 RNA 分子和推断基于结构的序列比对的最准确方法。拓扑独立叠加尤其相关，因为具有序列置换的结构相似的 RNA 就是证据，例如 tRNA 和 Y RNA。迄今为止，用于 RNA 3D 结构叠加的最先进方法依赖于复杂的启发式方法，并且尚未充分发挥拓扑独立叠加的潜力。最近，我们引入了用于 RNA 3D 模块无约束成对叠加的 ARTEM 方法，现在我们进一步开发了它来解决全局 RNA 3D 结构对齐问题。我们的新工具 ARTEMIS 在顺序和拓扑独立的 RNA 3D 结构叠加方面都明显优于最先进的工具。使用 ARTEMIS，我们发现了一个螺旋包装基序，它在各种非编码 RNA 中，包括多个核酶和核糖开关中，在不同的骨架拓扑背景下得以保留。我们预计，ARTEMIS 将对于阐明 RNA 3D 折叠景观和具有序列置换的基序至关重要，这些序列置换由于先前计算方法的限制，迄今为止仍未得到探索。
