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000303249 1001_ $$00009-0009-1463-3099$$aGuo, Wei$$b0
000303249 245__ $$aQueuosine is incorporated into precursor tRNA before splicing.
000303249 260__ $$a[London]$$bSpringer Nature$$c2025
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000303249 520__ $$aEach 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.
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000303249 650_7 $$057072-36-3$$2NLM Chemicals$$aNucleoside Q
000303249 650_7 $$2NLM Chemicals$$aRNA Precursors
000303249 650_7 $$09014-25-9$$2NLM Chemicals$$aRNA, Transfer
000303249 650_7 $$2NLM Chemicals$$aAnticodon
000303249 650_7 $$0EC 2.4.2.-$$2NLM Chemicals$$aPentosyltransferases
000303249 650_2 $$2MeSH$$aAnimals
000303249 650_2 $$2MeSH$$aRNA Splicing
000303249 650_2 $$2MeSH$$aNucleoside Q: metabolism
000303249 650_2 $$2MeSH$$aHumans
000303249 650_2 $$2MeSH$$aMice
000303249 650_2 $$2MeSH$$aRNA Precursors: metabolism
000303249 650_2 $$2MeSH$$aRNA Precursors: genetics
000303249 650_2 $$2MeSH$$aRNA, Transfer: metabolism
000303249 650_2 $$2MeSH$$aRNA, Transfer: genetics
000303249 650_2 $$2MeSH$$aCryoelectron Microscopy
000303249 650_2 $$2MeSH$$aIntrons: genetics
000303249 650_2 $$2MeSH$$aAnticodon: genetics
000303249 650_2 $$2MeSH$$aCaenorhabditis elegans: genetics
000303249 650_2 $$2MeSH$$aPentosyltransferases: metabolism
000303249 7001_ $$00000-0002-5607-7416$$aKaczmarczyk, Igor$$b1
000303249 7001_ $$00009-0007-0423-4049$$aKopietz, Kevin$$b2
000303249 7001_ $$aFlegler, Florian$$b3
000303249 7001_ $$00000-0001-7539-0427$$aRusso, Stefano$$b4
000303249 7001_ $$aCigirgan, Ege$$b5
000303249 7001_ $$aChramiec-Głąbik, Andrzej$$b6
000303249 7001_ $$00000-0003-3885-3845$$aKoziej, Łukasz$$b7
000303249 7001_ $$0P:(DE-He78)20f58a8a4fd3f952730ed9580f66f7fc$$aCirzi, Cansu$$b8
000303249 7001_ $$00000-0001-8158-9301$$aPeschek, Jirka$$b9
000303249 7001_ $$aReuter, Klaus$$b10
000303249 7001_ $$00000-0002-0154-0928$$aHelm, Mark$$b11
000303249 7001_ $$00000-0003-2815-7133$$aGlatt, Sebastian$$b12
000303249 7001_ $$aTuorto, Francesca$$b13
000303249 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-62220-z$$gVol. 16, no. 1, p. 7044$$n1$$p7044$$tNature Communications$$v16$$x2041-1723$$y2025
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