tRNA-derived second messengers confer bacterial immunity

  1. Luis E. Valentin-Alvarado
  2. Peter H. Yoon
  3. Santiago C. Lopez
  4. Yekaterina Shulgina
  5. Conner Langeberg
  6. Emily Armbruster
  7. Muhammad Moez Ur-Rehman
  8. Kenneth Loi
  9. Cyntia Taveneau
  10. Isabel Esain-Garcia
  11. Mert Koka
  12. Zeyuan Terry Zhang
  13. Dmitry Kashin
  14. Frank Schwede
  15. Gaetan Burgio
  16. Mitchell R. O’Connell
  17. Erin E. Doherty
  18. Jamie H. D. Cate
  19. Gavin J. Knott
  20. Jennifer A. Doudna
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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, 2TMβ, are co-encoded in an operon and are jointly required for bacteriophage defense. Upon target RNA recognition, Cas13 activates 2TMβ by producing mono- and dinucleotide messengers bearing 2′,3′-cyclic uridine phosphate ends by tRNA cleavage. Activated 2TMβ 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.

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  1. Mentioned by @pacyc184.bsky.social on Bluesky

    tRNA-derived second messengers confer bacterial immunity | bioRxiv

  2. Mentioned by @luisvalentin.bsky.social on Bluesky

    Massive thanks to P. Yoon and, S. Lopez, @kshulgina.bsky.social, @clangeberg.bsky.social, @knottrna.bsky.social , @doudna-lab.bsky.social and to all our collaborators. Now on @biorxivpreprint.bsky.social www.biorxiv.org/content/10.6... 11/11

  3. Mentioned by @biorxiv-microbiol.bsky.social on Bluesky

    tRNA-derived second messengers confer bacterial immunity https://www.biorxiv.org/content/10.64898/2026.10.06.756102v1

  4. Mentioned by @biorxivpreprint.bsky.social on Bluesky

    tRNA-derived second messengers confer bacterial immunity https://www.biorxiv.org/content/10.64898/2026.10.06.756102v1

  5. Version published to 10.64898/2026.10.06.756102v1 on bioRxiv