[{"external_id":{"pmid":["41501459"]},"PlanS_conform":"1","day":"29","oa_version":"Published Version","intvolume":"       649","publication_status":"published","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","doi":"10.1038/s41586-025-09852-9","publisher":"Springer Nature","type":"journal_article","year":"2026","department":[{"_id":"JaBr"}],"has_accepted_license":"1","article_processing_charge":"Yes (via OA deal)","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"publication":"Nature","citation":{"ista":"Dmytrenko O, Yuan B, Crosby KT, Krebel M, Chen X, Nowak JS, Chramiec-Głąbik A, Filani B, Gribling-Burrer A-S, van der Toorn W, von Kleist M, Achmedov T, Smyth RP, Glatt S, Bravo JPK, Heinz DW, Jackson RN, Beisel CL. 2026. RNA-triggered Cas12a3 cleaves tRNA tails to execute bacterial immunity. Nature. 649, 1312–1321.","ama":"Dmytrenko O, Yuan B, Crosby KT, et al. RNA-triggered Cas12a3 cleaves tRNA tails to execute bacterial immunity. <i>Nature</i>. 2026;649:1312-1321. doi:<a href=\"https://doi.org/10.1038/s41586-025-09852-9\">10.1038/s41586-025-09852-9</a>","ieee":"O. Dmytrenko <i>et al.</i>, “RNA-triggered Cas12a3 cleaves tRNA tails to execute bacterial immunity,” <i>Nature</i>, vol. 649. Springer Nature, pp. 1312–1321, 2026.","short":"O. Dmytrenko, B. Yuan, K.T. Crosby, M. Krebel, X. Chen, J.S. Nowak, A. Chramiec-Głąbik, B. Filani, A.-S. Gribling-Burrer, W. van der Toorn, M. von Kleist, T. Achmedov, R.P. Smyth, S. Glatt, J.P.K. Bravo, D.W. Heinz, R.N. Jackson, C.L. Beisel, Nature 649 (2026) 1312–1321.","apa":"Dmytrenko, O., Yuan, B., Crosby, K. T., Krebel, M., Chen, X., Nowak, J. S., … Beisel, C. L. (2026). RNA-triggered Cas12a3 cleaves tRNA tails to execute bacterial immunity. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-025-09852-9\">https://doi.org/10.1038/s41586-025-09852-9</a>","chicago":"Dmytrenko, Oleg, Biao Yuan, Kadin T. Crosby, Max Krebel, Xiye Chen, Jakub S. Nowak, Andrzej Chramiec-Głąbik, et al. “RNA-Triggered Cas12a3 Cleaves TRNA Tails to Execute Bacterial Immunity.” <i>Nature</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41586-025-09852-9\">https://doi.org/10.1038/s41586-025-09852-9</a>.","mla":"Dmytrenko, Oleg, et al. “RNA-Triggered Cas12a3 Cleaves TRNA Tails to Execute Bacterial Immunity.” <i>Nature</i>, vol. 649, Springer Nature, 2026, pp. 1312–21, doi:<a href=\"https://doi.org/10.1038/s41586-025-09852-9\">10.1038/s41586-025-09852-9</a>."},"supplementarymaterial":"yes","OA_type":"hybrid","author":[{"first_name":"Oleg","full_name":"Dmytrenko, Oleg","last_name":"Dmytrenko"},{"first_name":"Biao","last_name":"Yuan","full_name":"Yuan, Biao"},{"first_name":"Kadin T.","last_name":"Crosby","full_name":"Crosby, Kadin T."},{"first_name":"Max","last_name":"Krebel","full_name":"Krebel, Max"},{"first_name":"Xiye","full_name":"Chen, Xiye","last_name":"Chen"},{"full_name":"Nowak, Jakub S.","last_name":"Nowak","first_name":"Jakub S."},{"last_name":"Chramiec-Głąbik","full_name":"Chramiec-Głąbik, Andrzej","first_name":"Andrzej"},{"last_name":"Filani","full_name":"Filani, Bamidele","first_name":"Bamidele"},{"first_name":"Anne-Sophie","last_name":"Gribling-Burrer","full_name":"Gribling-Burrer, Anne-Sophie"},{"first_name":"Wiep","last_name":"van der Toorn","full_name":"van der Toorn, Wiep"},{"full_name":"von Kleist, Max","last_name":"von Kleist","first_name":"Max"},{"last_name":"Achmedov","full_name":"Achmedov, Tatjana","first_name":"Tatjana"},{"last_name":"Smyth","full_name":"Smyth, Redmond P.","first_name":"Redmond P."},{"first_name":"Sebastian","full_name":"Glatt, Sebastian","last_name":"Glatt"},{"last_name":"Bravo","id":"96aecfa5-8931-11ee-af30-aa6a5d6eee0e","full_name":"Bravo, Jack Peter Kelly","first_name":"Jack Peter Kelly","orcid":"0000-0003-0456-0753"},{"first_name":"Dirk W.","full_name":"Heinz, Dirk W.","last_name":"Heinz"},{"first_name":"Ryan N.","full_name":"Jackson, Ryan N.","last_name":"Jackson"},{"last_name":"Beisel","full_name":"Beisel, Chase L.","first_name":"Chase L."}],"pmid":1,"ddc":["570"],"researchdata_availability":"yes","abstract":[{"lang":"eng","text":"In all domains of life, tRNAs mediate the transfer of genetic information from mRNAs to proteins. As their depletion suppresses translation and, consequently, viral replication, tRNAs represent long-standing and increasingly recognized targets of innate immunity1,2,3,4,5. Here we report Cas12a3 effector nucleases from type V CRISPR–Cas adaptive immune systems in bacteria that preferentially cleave tRNAs after recognition of target RNA. Cas12a3 orthologues belong to one of two previously unreported nuclease clades that exhibit RNA-mediated cleavage of non-target RNA, and are distinct from all other known type V systems. Through cell-based and biochemical assays and direct RNA sequencing, we demonstrate that recognition of a complementary target RNA by the CRISPR RNA triggers Cas12a3 to cleave the conserved 5′-CCA-3′ tail of diverse tRNAs to drive growth arrest and anti-phage defence. Cryogenic electron microscopy structures further revealed a distinct tRNA-loading domain that positions the tRNA tail in the RuvC active site of the nuclease. By designing synthetic reporters that mimic the tRNA acceptor stem and tail, we expanded the capacity of current CRISPR-based diagnostics for multiplexed RNA detection. Overall, these findings reveal widespread tRNA inactivation as a previously unrecognized CRISPR-based immune strategy that broadens the application space of the existing CRISPR toolbox."}],"publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"article_type":"original","das_tickbox":"1","acknowledgement":"We thank Ł. Koziej for processing of the initial cryo-EM datasets, S. Schmelz for support in cryo-EM, A. Gatzemeier for assistance in the purification of dBa1Cas12a3, R. Rarose for support with the in vitro RNA experiments, M. Kaminski for providing purified PsmCas13b protein, L. Schönemann for protein purification, and C. Krempl and S. Backesfor providing the RSV and influenza A transcript-encoding plasmids. This work was supported through funding by the European Research Council (101001394 to S.G.; 865973 and 101158249 to C.L.B.), the R. Gaurth Hansen Family (to R.N.J.), the National Institutes of Health (R35GM138080 to R.N.J.), the PostDoc Plus Program from the Graduate School of Life Sciences at Julius-Maximilians-Universität Würzburg (to O.D.), and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy–The Berlin Mathematics Research Center MATH+ (EXC−2046/1, project ID: 390685689 to M.v.K.). Open access funding provided by Helmholtz-Zentrum für Infektionsforschung GmbH (HZI).","fulldoi":"https://doi.org/10.1038/s41586-025-09852-9","file":[{"checksum":"f6b40af573fc7c0c0195e1428b1d0143","file_size":28253320,"success":1,"date_updated":"2026-07-27T10:35:26Z","relation":"main_file","file_name":"2026_Nature_Dmytrenko.pdf","date_created":"2026-07-27T10:35:26Z","creator":"dernst","content_type":"application/pdf","access_level":"open_access","file_id":"22415"}],"date_created":"2026-01-08T07:57:17Z","OA_place":"publisher","date_updated":"2026-07-27T10:36:28Z","quality_controlled":"1","date_published":"2026-01-29T00:00:00Z","scopus_import":"1","_id":"20963","month":"01","title":"RNA-triggered Cas12a3 cleaves tRNA tails to execute bacterial immunity","status":"public","volume":649,"page":"1312-1321","file_date_updated":"2026-07-27T10:35:26Z","dataavailabilitystatement":"The Illumina-based PFS screen data and the direct RNA Nanopore sequencing reads have been deposited into the European Nucleotide Archive under accession code PRJEB88250 (https://www.ebi.ac.uk/ena/browser/view/PRJEB88250). Models and associated cryo-EM maps have been deposited into the Electron Microscopy Data Bank (EMD) and PDB databases with the following accession codes: Ba1Cas12a3 binary complex (EMD-52275; PDB: 9HLX); Ba1Cas12a3 ternary complex (EMD-52287; PDB: 9HM6); Ba1Cas12a3 quaternary complex at pre-cleavage state (EMD-52285; PDB: 9HM4); and Ba1Cas12a3 quaternary complex at post-cleavage state (EMD-52286; PDB: 9HM5). Raw gel images are included as Supplementary Fig. 1. Source data are provided with this paper.","oa":1}]