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Queuosine is incorporated into precursor tRNA before splicing

Author

Listed:
  • Wei Guo

    (Heidelberg University
    DKFZ-ZMBH Alliance
    Heidelberg University)

  • Igor Kaczmarczyk

    (Jagiellonian University
    Jagiellonian University)

  • Kevin Kopietz

    (Johannes Gutenberg-University Mainz)

  • Florian Flegler

    (Philipps-Universität Marburg)

  • Stefano Russo

    (Heidelberg University
    DKFZ-ZMBH Alliance
    Heidelberg University)

  • Ege Cigirgan

    (Heidelberg University)

  • Andrzej Chramiec-Głąbik

    (Jagiellonian University)

  • Łukasz Koziej

    (Jagiellonian University)

  • Cansu Cirzi

    (German Cancer Research Center (DKFZ))

  • Jirka Peschek

    (Heidelberg University)

  • Klaus Reuter

    (Philipps-Universität Marburg)

  • Mark Helm

    (Johannes Gutenberg-University Mainz)

  • Sebastian Glatt

    (Jagiellonian University
    University of Veterinary Medicine Vienna)

  • Francesca Tuorto

    (DKFZ-ZMBH Alliance
    Heidelberg University)

Abstract

Each newly transcribed tRNA molecule must undergo processing and receive modifications to become functional. Queuosine (Q) is a tRNA modification present at position 34 of four tRNAs with “GUN” anticodons. Among these, the precursor of tRNATyr carries an intronic sequence within the anticodon loop that is removed by an essential non-canonical splicing event. The functional and temporal coupling between tRNA-splicing and Q-incorporation remains elusive. Here, we demonstrate in vitro and in vivo that intron-containing precursors of tRNATyr are modified with Q or with the Q-derivative galactosyl-queuosine (galQ) before being spliced. We show that this order of events is conserved in mouse, human, flies and worms. Using single particle cryo-EM, we confirm that pre-tRNATyr is a bona fide substrate of the QTRT1/2 complex, which catalyzes the incorporation of Q into the tRNA. Our results elucidate the hierarchical interplay that coordinates Q-incorporation and splicing in eukaryotic tRNAs, providing a relevant but unappreciated aspect of the cellular tRNA maturation process.

Suggested Citation

  • Wei Guo & Igor Kaczmarczyk & Kevin Kopietz & Florian Flegler & Stefano Russo & Ege Cigirgan & Andrzej Chramiec-Głąbik & Łukasz Koziej & Cansu Cirzi & Jirka Peschek & Klaus Reuter & Mark Helm & Sebasti, 2025. "Queuosine is incorporated into precursor tRNA before splicing," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62220-z
    DOI: 10.1038/s41467-025-62220-z
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