TY  - JOUR
AU  - Cirzi, Cansu
AU  - Dyckow, Julia
AU  - Legrand, Carine
AU  - Schott, Johanna
AU  - Guo, Wei
AU  - Perez Hernandez, Daniel
AU  - Hisaoka, Miharu
AU  - Parlato, Rosanna
AU  - Pitzer, Claudia
AU  - van der Hoeven, Franciscus
AU  - Dittmar, Gunnar
AU  - Helm, Mark
AU  - Stoecklin, Georg
AU  - Schirmer, Lucas
AU  - Lyko, Frank
AU  - Tuorto, Francesca
TI  - Queuosine-tRNA promotes sex-dependent learning and memory formation by maintaining codon-biased translation elongation speed.
JO  - The EMBO journal
VL  - 42
IS  - 19
SN  - 0261-4189
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DKFZ-2023-01699
SP  - e112507
PY  - 2023
N1  - #EA:A130#LA:A130# / DKFZ-ZMBH Alliance / 2023 Oct 4;42(19):e112507
AB  - 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.
KW  - learning and memory (Other)
KW  - protein translation (Other)
KW  - queuosine (Other)
KW  - sex bias (Other)
KW  - tRNA modifications (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37609797
DO  - DOI:10.15252/embj.2022112507
UR  - https://inrepo02.dkfz.de/record/278728
ER  -