{
  "abstract": "Bacterial small-molecule messengers that function in diverse immune signaling pathways have been thought to derive strictly from biosynthesis using nucleotide and cofactor substrates. Here we report a nuclease-driven immune signaling pathway in which tRNA cleavage generates a specific small molecule that triggers cell death in response to RNA-guided transcript recognition in prokaryotes. We identify a class of type VI-B CRISPR systems in which the RNA-guided nuclease Cas13 and its accessory transmembrane protein, 2TM{beta}, are co-encoded in an operon and are jointly required for bacteriophage defense. Upon target RNA recognition, Cas13 activates 2TM{beta} by producing mono- and dinucleotide messengers bearing 2',3'-cyclic uridine phosphate ends by tRNA cleavage. Activated 2TM{beta} destroys infected cells by forming a multimeric complex that disrupts cell membranes to mediate cell death. These findings demonstrate RNA-programmed tRNA cleavage for second-messenger biogenesis, revealing a new logic for prokaryotic immune signaling.",
  "abstract_shown": true,
  "affiliations": [
    "Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA; Department of Molecular and Cell Biology, University of California, Berkel"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "name": "L. E. Valentin-Alvarado"
    },
    {
      "name": "P. H. Yoon"
    },
    {
      "name": "S. C. Lopez"
    },
    {
      "name": "Y. Shulgina"
    },
    {
      "name": "C. Langeberg"
    },
    {
      "name": "E. Armbruster"
    },
    {
      "name": "M. M. Ur-Rehman"
    },
    {
      "name": "K. Loi"
    },
    {
      "name": "C. Taveneau"
    },
    {
      "name": "I. Esain-Garcia"
    },
    {
      "name": "M. Koka"
    },
    {
      "name": "Z. T. Zhang"
    },
    {
      "name": "D. Kashin"
    },
    {
      "name": "F. Schwede"
    },
    {
      "name": "G. Burgio"
    },
    {
      "name": "M. R. OConnell"
    },
    {
      "name": "E. E. Doherty"
    },
    {
      "name": "J. H. D. Cate"
    },
    {
      "name": "G. J. Knott"
    },
    {
      "affs": [
        0
      ],
      "name": "J. A. Doudna"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d97s3n69vna49.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.06.756102",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.756102v1.full",
  "id": "d97s3n69vna49",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.756102v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "1312|CRISPR and Genetic Engineering"
    ]
  ],
  "openalex": "W7221067405",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.756102v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d97s3n69vna49.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:48Z",
      "native_id": "10.64898/2026.10.06.756102",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.06.756102v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "tRNA-derived second messengers confer bacterial immunity",
  "title_text": "tRNA-derived second messengers confer bacterial immunity",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:48Z",
  "url": "https://research.draconitic.com/paper/d97s3n69vna49",
  "venue": "bioRxiv",
  "versions": []
}