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TitleQueuosine is incorporated into precursor tRNA before splicing.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 7044, Year 2025
Publish dateJul 31, 2025
AuthorsWei Guo / Igor Kaczmarczyk / Kevin Kopietz / Florian Flegler / Stefano Russo / Ege Cigirgan / Andrzej Chramiec-Głąbik / Łukasz Koziej / Cansu Cirzi / Jirka Peschek / Klaus Reuter / Mark Helm / Sebastian Glatt / Francesca Tuorto /
PubMed AbstractEach 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" ...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 tRNA 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 tRNA 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-tRNA 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.
External linksNat Commun / PubMed:40745156 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.1 Å
Structure data

52308

9hn7

EMDB-52308, PDB-9hn7:
Mouse QTRT1/2 in complex with mouse tRNA-Tyr
Method: EM (single particle) / Resolution: 2.9 Å

52309

9hn9

EMDB-52309, PDB-9hn9:
Mouse QTRT1/2 in complex with mouse pre-tRNA-Tyr-1-4
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-9DG:
9-DEAZAGUANINE

Source
  • mus musculus (house mouse)
KeywordsRNA BINDING PROTEIN / queuosine / tRNA / QTRT1/2 / tRNA modification

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