A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA

作者：Man Lu, Zhiqiang Cao, Luoan Xiong, Hongying Deng, Kangkang Ma, Ning Liu, Yanding Qin, Shen‐Bo Chen, Jun‐Hu Chen, Yao Li, Yijin Liu, Zhongbo Yu · 发表于：Communications Biology · 年份：2025 · DOI：10.1038/s42003-025-07600-3 · 被引用次数：5 · 研究领域：RNA and protein synthesis mechanisms、Advanced biosensing and bioanalysis techniques、DNA and Nucleic Acid Chemistry

Ribozymes, widely found in prokaryotes and eukaryotes, target nucleic acids and can be engineered as biotechnical tools or for gene regulation or immune therapy. Among them, hammerhead is the smallest and best characterized ribozyme. However, the structure and biochemical data of ribozymes have been disagreed on, making the understanding of its catalysis mechanism a longstanding issue. Particularly, the role of conformational dynamics in ribozyme catalysis remains elusive. Here, we use single-molecule magnetic tweezers to reveal a concerted catalysis mechanism of mechanical conformational selection for a mini hammerhead ribozyme against a viral RNA sequence from the SARS-CoV-2. We identify a conformational set containing five mechanical conformers of the mini ribozyme, where magnesium ions select the active one. Our results are supported by molecular dynamics simulations. Our understanding of the RNA catalytic mechanism will be beneficial for ribozyme's biotechnological applications and as potential therapeutics against RNA viruses.