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Here, we show that domain of unknown function 4062 (DUF4062) is a widespread family of TIR-like NADases that hydrolyze NAD\n                  <jats:sup>+<\/jats:sup>\n                  to ADP-ribose and nicotinamide. In bacteria, DUF4062 homologs form a previously unrecognized antiphage defense system, which we name Swaro\u017cyc, that assembles with the phage portal into a supramolecular NADase complex to induce abortive infection. In eukaryotes, DUF4062 is found in TEP1, which we demonstrate functions as an active NADase within the RNA vault, an enigmatic organelle-like structure. Single-particle cryo-electron microscopy reveals ADP-ribose bound within the shoulder of both reconstituted and human brain vaults, while cryo-electron tomography positions TEP1 along the central axis at the shoulder. Thus, TEP1, like bacterial Swaro\u017cyc, functions by depleting NAD\n                  <jats:sup>+<\/jats:sup>\n                  , providing new insight into the long-standing mystery of vault function.\n                <\/jats:p>","DOI":"10.64898\/2026.05.01.722283","type":"posted-content","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T04:55:13Z","timestamp":1778043313000},"source":"Crossref","is-referenced-by-count":2,"title":["TIR-like NADases act in bacterial immunity and the RNA vault"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0010-0733","authenticated-orcid":false,"given":"Adam","family":"Osinski","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center; Dallas, TX, 75390, USA"},{"name":"Howard Hughes Medical Institute, University of Texas Southwestern Medical Center; Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Mayro","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center; Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor A.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center; Dallas, TX, 75390, USA"},{"name":"Howard Hughes Medical Institute, University of Texas Southwestern Medical Center; Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6695-7070","authenticated-orcid":false,"given":"Jason","family":"Schrad","sequence":"additional","affiliation":[{"name":"Center for Alzheimer\u2019s and Neurodegenerative Diseases, Peter O\u2019Donnell Jr. Brain Institute, Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2167-445X","authenticated-orcid":false,"given":"Hannah","family":"Choi","sequence":"additional","affiliation":[{"name":"Center for Alzheimer\u2019s and Neurodegenerative Diseases, Peter O\u2019Donnell Jr. Brain Institute, Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7529-4643","authenticated-orcid":false,"given":"Diana R.","family":"Tomchick","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center; Dallas, TX, 75390, USA"},{"name":"Department of Biophysics, University of Texas Southwestern Medical Center; Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Paw\u0142owski","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center; Dallas, TX, 75390, USA"},{"name":"Howard Hughes Medical Institute, University of Texas Southwestern Medical Center; Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1545-8925","authenticated-orcid":false,"given":"Kevin","family":"Forsberg","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Texas Southwestern Medical Center; Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9752-7287","authenticated-orcid":false,"given":"Sarah H.","family":"Shahmoradian","sequence":"additional","affiliation":[{"name":"Center for Alzheimer\u2019s and Neurodegenerative Diseases, Peter O\u2019Donnell Jr. Brain Institute, Dallas, TX, 75390, USA"},{"name":"Department of Biophysics, University of Texas Southwestern Medical Center; Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9735-4678","authenticated-orcid":false,"given":"Vincent S.","family":"Tagliabracci","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center; Dallas, TX, 75390, USA"},{"name":"Howard Hughes Medical Institute, University of Texas Southwestern Medical Center; Dallas, TX, 75390, USA"},{"name":"Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center; Dallas, Texas, 75390, USA"},{"name":"Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center; Dallas, Texas, 75390, 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