{"title":"功能性RNA分裂推动了转座子V型CRISPR-Cas系统的进化出现","authors":"Shuai Jin, Zixu Zhu, Yunjia Li, Shouyue Zhang, Yijing Liu, Danyuan Li, Yuanqing Li, Yingfeng Luo, Zhiheng Cheng, Kevin Tianmeng Zhao, Qiang Gao, Guanglei Yang, Hongchao Li, Ronghong Liang, Rui Zhang, Jin-Long Qiu, Yong E. Zhang, Jun-Jie Gogo Liu, Caixia Gao","doi":"10.1016/j.cell.2025.09.004","DOIUrl":null,"url":null,"abstract":"Transposon-encoded TnpB nucleases gave rise to type V CRISPR-Cas12 effectors through multiple independent domestication events. These systems use different RNA molecules as guides for DNA targeting: transposon-derived right-end RNAs (reRNAs or omega RNAs) for TnpB and CRISPR RNAs for type V CRISPR-Cas systems. However, the molecular mechanisms bridging transposon activity and CRISPR immunity remain unclear. We identify TranCs (transposon-CRISPR intermediates) derived from distinct IS605- or IS607-TnpB lineages. TranCs utilize both CRISPR RNAs and reRNAs to direct DNA cleavage. The cryoelectron microscopy (cryo-EM) structure of LaTranC from <em>Lawsonibacter sp.</em> closely resembles that of the ISDra2 TnpB complex; however, unlike a single-molecule reRNA, the LaTranC guide RNA is functionally split into a tracrRNA and crRNA. An engineered RNA split of ISDra2 TnpB enabled activity with a CRISPR array. These findings indicate that functional RNA splitting was the primary molecular event driving the emergence of diverse type V CRISPR-Cas systems from transposons.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"1 1","pages":""},"PeriodicalIF":42.5000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Functional RNA splitting drove the evolutionary emergence of type V CRISPR-Cas systems from transposons\",\"authors\":\"Shuai Jin, Zixu Zhu, Yunjia Li, Shouyue Zhang, Yijing Liu, Danyuan Li, Yuanqing Li, Yingfeng Luo, Zhiheng Cheng, Kevin Tianmeng Zhao, Qiang Gao, Guanglei Yang, Hongchao Li, Ronghong Liang, Rui Zhang, Jin-Long Qiu, Yong E. Zhang, Jun-Jie Gogo Liu, Caixia Gao\",\"doi\":\"10.1016/j.cell.2025.09.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Transposon-encoded TnpB nucleases gave rise to type V CRISPR-Cas12 effectors through multiple independent domestication events. These systems use different RNA molecules as guides for DNA targeting: transposon-derived right-end RNAs (reRNAs or omega RNAs) for TnpB and CRISPR RNAs for type V CRISPR-Cas systems. However, the molecular mechanisms bridging transposon activity and CRISPR immunity remain unclear. We identify TranCs (transposon-CRISPR intermediates) derived from distinct IS605- or IS607-TnpB lineages. TranCs utilize both CRISPR RNAs and reRNAs to direct DNA cleavage. The cryoelectron microscopy (cryo-EM) structure of LaTranC from <em>Lawsonibacter sp.</em> closely resembles that of the ISDra2 TnpB complex; however, unlike a single-molecule reRNA, the LaTranC guide RNA is functionally split into a tracrRNA and crRNA. An engineered RNA split of ISDra2 TnpB enabled activity with a CRISPR array. These findings indicate that functional RNA splitting was the primary molecular event driving the emergence of diverse type V CRISPR-Cas systems from transposons.\",\"PeriodicalId\":9656,\"journal\":{\"name\":\"Cell\",\"volume\":\"1 1\",\"pages\":\"\"},\"PeriodicalIF\":42.5000,\"publicationDate\":\"2025-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cell.2025.09.004\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cell.2025.09.004","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Functional RNA splitting drove the evolutionary emergence of type V CRISPR-Cas systems from transposons
Transposon-encoded TnpB nucleases gave rise to type V CRISPR-Cas12 effectors through multiple independent domestication events. These systems use different RNA molecules as guides for DNA targeting: transposon-derived right-end RNAs (reRNAs or omega RNAs) for TnpB and CRISPR RNAs for type V CRISPR-Cas systems. However, the molecular mechanisms bridging transposon activity and CRISPR immunity remain unclear. We identify TranCs (transposon-CRISPR intermediates) derived from distinct IS605- or IS607-TnpB lineages. TranCs utilize both CRISPR RNAs and reRNAs to direct DNA cleavage. The cryoelectron microscopy (cryo-EM) structure of LaTranC from Lawsonibacter sp. closely resembles that of the ISDra2 TnpB complex; however, unlike a single-molecule reRNA, the LaTranC guide RNA is functionally split into a tracrRNA and crRNA. An engineered RNA split of ISDra2 TnpB enabled activity with a CRISPR array. These findings indicate that functional RNA splitting was the primary molecular event driving the emergence of diverse type V CRISPR-Cas systems from transposons.
期刊介绍:
Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO).
The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries.
In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.