@article{f34008a1b2ec4444b74ff9f31074a7a6,
title = "Queuosine-tRNA promotes sex-dependent learning and memory formation by maintaining codon-biased translation elongation speed",
abstract = "Queuosine (Q) is a modified nucleoside at the wobble position of specific tRNAs. In mammals, queuosinylation is facilitated by queuine uptake from the gut microbiota and is introduced into tRNA by the QTRT1-QTRT2 enzyme complex. By establishing a Qtrt1 knockout mouse model, we discovered that the loss of Q-tRNA leads to learning and memory deficits. Ribo-Seq analysis in the hippocampus of Qtrt1-deficient mice revealed not only stalling of ribosomes on Q-decoded codons, but also a global imbalance in translation elongation speed between codons that engage in weak and strong interactions with their cognate anticodons. While Q-dependent molecular and behavioral phenotypes were identified in both sexes, female mice were affected more severely than males. Proteomics analysis confirmed deregulation of synaptogenesis and neuronal morphology. Together, our findings provide a link between tRNA modification and brain functions and reveal an unexpected role of protein synthesis in sex-dependent cognitive performance.",
keywords = "learning and memory, protein translation, queuosine, sex bias, tRNA modifications",
author = "Cansu Cirzi and Julia Dyckow and Carine Legrand and Johanna Schott and Wei Guo and {Perez Hernandez}, Daniel and Miharu Hisaoka and Rosanna Parlato and Claudia Pitzer and {van der Hoeven}, Franciscus and Gunnar Dittmar and Mark Helm and Georg Stoecklin and Lucas Schirmer and Frank Lyko and Francesca Tuorto",
note = "Funding Information: We would like to thank Maria Giuseppina Miano and Sebastian Leidel for their valuable discussions and comments. We thank Anna Kiryk for the help with IntelliCage analysis. We also thank Kai Volz, Doris Linder, Thi Bach Nga Ly‐Hartig, Barbara Kurpiers, and Dr. Annika Kotter for technical support. This work was funded by grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project numbers: 439669440 TRR319 RMaP TP C03 to M.H., A04 to G.S., A01 to F.L., and A06 to F.T., and projects TU5371‐2 to F.T., SPP 1784 to M.H. and F.L.. L.S. received intramural funding from Heidelberg University, and research grants from the Hertie Foundation (medMS MyLab, P1180016), the European Research Council (“DecOmPress” ERC StG), and the German Research Foundation (SCHI 1330/2‐1). F.T. was supported by the Institute of Genetics and Biophysics A. Buzzati‐Traverso, The National Research Council of Italy. Open Access funding enabled and organized by Projekt DEAL. Publisher Copyright: {\textcopyright} 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.",
year = "2023",
month = oct,
day = "4",
doi = "10.15252/embj.2022112507",
language = "English",
volume = "42",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "EMBO Press",
number = "19",
}