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This is a In Vitro Study study (also classified as: Observational).

September 10, 2025Open Access

Queuosine is incorporated into precursor tRNA before splicing

Key Points

Queuosine incorporation into precursor tRNA occurs prior to splicing, indicating a crucial modification step.
In vitro and in vivo experiments show that intron-containing precursor tRNA Tyr is modified with queuosine before splicing.
Using single particle cryo-EM, we confirmed that queuosine modification involves the QTRT1/2 complex as a substrate.
This research highlights a critical aspect of the tRNA maturation process in eukaryotic organisms.

Abstract

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 tRNA Tyr 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 Tyr 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 Tyr 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.

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