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Queuosine‐tRNA promotes sex‐dependent learning and memory formation by maintaining codon‐biased translation elongation speed

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 lo...

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Main Authors: Cirzi, Cansu (Author) , Dyckow, Julia (Author) , Legrand, Carine (Author) , Schott, Johanna (Author) , Guo, Wei (Author) , Perez Hernandez, Daniel (Author) , Hisaoka, Miharu (Author) , Parlato, Rosanna (Author) , Pitzer, Claudia (Author) , van der Hoeven, Franciscus (Author) , Dittmar, Gunnar (Author) , Helm, Mark (Author) , Stoecklin, Georg (Author) , Schirmer, Lucas (Author) , Lyko, Frank (Author) , Tuorto, Francesca (Author)
Format: Article (Journal)
Language:English
Published: 23 August 2023
In: The EMBO journal
Year: 2023, Volume: 42, Issue: 19, Pages: 1-20
ISSN:1460-2075
DOI:10.15252/embj.2022112507
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.15252/embj.2022112507
Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.15252/embj.2022112507
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Author Notes:Cansu Cirzi, Julia Dyckow, Carine Legrand, Johanna Schott, Wei Guo, Daniel Perez Hernandez, Miharu Hisaoka, Rosanna Parlato, Claudia Pitzer, Franciscus van der Hoeven, Gunnar Dittmar, Mark Helm, Georg Stoecklin, Lucas Schirmer, Frank Lyko & Francesca Tuorto
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Summary: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.
Item Description:Gesehen am 24.07.2024
Physical Description:Online Resource
ISSN:1460-2075
DOI:10.15252/embj.2022112507

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