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

Publication type:
Journal article
Metadata:
Autoren
  • 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
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:001052644600001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.15252/embj.2022112507
eISSN
1460-2075
Externe Identifier
  • Clarivate Analytics Document Solution ID: T3JP7
  • PubMed Identifier: 37609797
ISSN
0261-4189
Ausgabe der Veröffentlichung
19
Zeitschrift
EMBO JOURNAL
Schlüsselwörter
  • learning and memory
  • protein translation
  • queuosine
  • sex bias
  • tRNA modifications
Datum der Veröffentlichung
2023
Status
Published
Titel
Queuosine-tRNA promotes sex-dependent learning and memory formation by maintaining codon-biased translation elongation speed
Sub types
  • Article
Ausgabe der Zeitschrift
42

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>Qtrt1</jats:italic> knockout mouse model, we discovered that the loss of Q‐tRNA leads to learning and memory deficits. Ribo‐Seq analysis in the hippocampus of <jats:italic>Qtrt1</jats:italic>‐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.</jats:p>
Autoren
  • 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
DOI
10.15252/embj.2022112507
eISSN
1460-2075
ISSN
0261-4189
Ausgabe der Veröffentlichung
19
Zeitschrift
The EMBO Journal
Sprache
en
Online publication date
2023
Datum der Veröffentlichung
2023
Status
Published
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.15252/embj.2022112507
Datum der Datenerfassung
2023
Titel
<scp>Queuosine‐tRNA</scp> promotes sex‐dependent learning and memory formation by maintaining codon‐biased translation elongation speed
Ausgabe der Zeitschrift
42

Data source: Crossref

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.
Addresses
  • Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Autoren
  • 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
DOI
10.15252/embj.2022112507
eISSN
1460-2075
Externe Identifier
  • PubMed Identifier: 37609797
  • PubMed Central ID: PMC10548180
Open access
true
ISSN
0261-4189
Ausgabe der Veröffentlichung
19
Zeitschrift
The EMBO journal
Schlüsselwörter
  • Animals
  • Mammals
  • Mice
  • Codon
  • RNA, Transfer
  • Anticodon
  • Nucleoside Q
  • Protein Biosynthesis
  • Female
Sprache
eng
Medium
Print-Electronic
Online publication date
2023
Open access status
Open Access
Paginierung
e112507
Datum der Veröffentlichung
2023
Status
Published
Publisher licence
CC BY-NC-ND
Datum der Datenerfassung
2023
Titel
Queuosine-tRNA promotes sex-dependent learning and memory formation by maintaining codon-biased translation elongation speed.
Sub types
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
42

Files

https://onlinelibrary.wiley.com/doi/pdfdirect/10.15252/embj.2022112507 https://europepmc.org/articles/PMC10548180?pdf=render

Data source: Europe PubMed Central

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.
Date of acceptance
2023
Autoren
  • 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
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/37609797
DOI
10.15252/embj.2022112507
eISSN
1460-2075
Externe Identifier
  • PubMed Central ID: PMC10548180
Ausgabe der Veröffentlichung
19
Zeitschrift
EMBO J
Schlüsselwörter
  • learning and memory
  • protein translation
  • queuosine
  • sex bias
  • tRNA modifications
  • Female
  • Mice
  • Animals
  • Nucleoside Q
  • RNA, Transfer
  • Anticodon
  • Protein Biosynthesis
  • Codon
  • Mammals
Sprache
eng
Country
England
Paginierung
e112507
Datum der Veröffentlichung
2023
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2023
Titel
Queuosine-tRNA promotes sex-dependent learning and memory formation by maintaining codon-biased translation elongation speed.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
42

Data source: PubMed

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