TY  - JOUR
AU  - Guo, Wei
AU  - Kaczmarczyk, Igor
AU  - Kopietz, Kevin
AU  - Flegler, Florian
AU  - Russo, Stefano
AU  - Cigirgan, Ege
AU  - Chramiec-Głąbik, Andrzej
AU  - Koziej, Łukasz
AU  - Cirzi, Cansu
AU  - Peschek, Jirka
AU  - Reuter, Klaus
AU  - Helm, Mark
AU  - Glatt, Sebastian
AU  - Tuorto, Francesca
TI  - Queuosine is incorporated into precursor tRNA before splicing.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-01594
SP  - 7044
PY  - 2025
N1  - DKFZ-ZMBH Alliance
AB  - 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.
KW  - Animals
KW  - RNA Splicing
KW  - Nucleoside Q: metabolism
KW  - Humans
KW  - Mice
KW  - RNA Precursors: metabolism
KW  - RNA Precursors: genetics
KW  - RNA, Transfer: metabolism
KW  - RNA, Transfer: genetics
KW  - Cryoelectron Microscopy
KW  - Introns: genetics
KW  - Anticodon: genetics
KW  - Caenorhabditis elegans: genetics
KW  - Pentosyltransferases: metabolism
KW  - Nucleoside Q (NLM Chemicals)
KW  - RNA Precursors (NLM Chemicals)
KW  - RNA, Transfer (NLM Chemicals)
KW  - Anticodon (NLM Chemicals)
KW  - Pentosyltransferases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40745156
DO  - DOI:10.1038/s41467-025-62220-z
UR  - https://inrepo02.dkfz.de/record/303249
ER  -