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@ARTICLE{Guo:303249,
author = {W. Guo and I. Kaczmarczyk and K. Kopietz and F. Flegler and
S. Russo and E. Cigirgan and A. Chramiec-Głąbik and Ł.
Koziej and C. Cirzi$^*$ and J. Peschek and K. Reuter and M.
Helm and S. Glatt and F. Tuorto},
title = {{Q}ueuosine is incorporated into precursor t{RNA} before
splicing.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-01594},
pages = {7044},
year = {2025},
note = {DKFZ-ZMBH Alliance},
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.},
keywords = {Animals / RNA Splicing / Nucleoside Q: metabolism / Humans
/ Mice / RNA Precursors: metabolism / RNA Precursors:
genetics / RNA, Transfer: metabolism / RNA, Transfer:
genetics / Cryoelectron Microscopy / Introns: genetics /
Anticodon: genetics / Caenorhabditis elegans: genetics /
Pentosyltransferases: metabolism / Nucleoside Q (NLM
Chemicals) / RNA Precursors (NLM Chemicals) / RNA, Transfer
(NLM Chemicals) / Anticodon (NLM Chemicals) /
Pentosyltransferases (NLM Chemicals)},
cin = {A130},
ddc = {500},
cid = {I:(DE-He78)A130-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40745156},
doi = {10.1038/s41467-025-62220-z},
url = {https://inrepo02.dkfz.de/record/303249},
}