A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA
Abstract 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...
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07600-3 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Man Lu |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-13cada01656540c4881566897a549712 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-13cada01656540c4881566897a5497122025-02-09T12:50:29ZengNature PortfolioCommunications Biology2399-36422025-02-01811810.1038/s42003-025-07600-3A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNAMan Lu0Zhiqiang Cao1Luoan Xiong2Hongying Deng3Kangkang Ma4Ning Liu5Yanding Qin6Shen-Bo Chen7Jun-Hu Chen8Yao Li9Yijin Liu10Zhongbo Yu11State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Pharmacy, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Pharmacy, Nankai UniversitySchool of Physics and Key Laboratory of Functional Polymer Materials of Ministry of Education, Nankai University, and Collaborative Innovation Center of Chemical Science and EngineeringState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, and College of Pharmacy, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Pharmacy, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Nankai UniversityCollege of Artificial Intelligence, Nankai UniversityNational Institute of Parasitic Diseases, Chinese Center for Diseases Control and Prevention (Chinese Center for Tropical Diseases Research), National Health Commission of the People’s Republic of China (NHC) Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical DiseasesNational Institute of Parasitic Diseases, Chinese Center for Diseases Control and Prevention (Chinese Center for Tropical Diseases Research), National Health Commission of the People’s Republic of China (NHC) Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical DiseasesSchool of Physics and Key Laboratory of Functional Polymer Materials of Ministry of Education, Nankai University, and Collaborative Innovation Center of Chemical Science and EngineeringState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, and College of Pharmacy, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Pharmacy, Nankai UniversityAbstract 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.https://doi.org/10.1038/s42003-025-07600-3 |
| spellingShingle | 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 A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA Communications Biology |
| title | A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA |
| title_full | A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA |
| title_fullStr | A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA |
| title_full_unstemmed | A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA |
| title_short | A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA |
| title_sort | hammerhead ribozyme selects mechanically stable conformations for catalysis against viral rna |
| url | https://doi.org/10.1038/s42003-025-07600-3 |
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