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000278728 1001_ $$0P:(DE-He78)20f58a8a4fd3f952730ed9580f66f7fc$$aCirzi, Cansu$$b0$$eFirst author
000278728 245__ $$aQueuosine-tRNA promotes sex-dependent learning and memory formation by maintaining codon-biased translation elongation speed.
000278728 260__ $$aHoboken, NJ [u.a.]$$bWiley$$c2023
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000278728 520__ $$aQueuosine (Q) is a modified nucleoside at the wobble position of specific tRNAs. In mammals, queuosinylation is facilitated by queuine uptake from the gut microbiota and is introduced into tRNA by the QTRT1-QTRT2 enzyme complex. By establishing a Qtrt1 knockout mouse model, we discovered that the loss of Q-tRNA leads to learning and memory deficits. Ribo-Seq analysis in the hippocampus of Qtrt1-deficient mice revealed not only stalling of ribosomes on Q-decoded codons, but also a global imbalance in translation elongation speed between codons that engage in weak and strong interactions with their cognate anticodons. While Q-dependent molecular and behavioral phenotypes were identified in both sexes, female mice were affected more severely than males. Proteomics analysis confirmed deregulation of synaptogenesis and neuronal morphology. Together, our findings provide a link between tRNA modification and brain functions and reveal an unexpected role of protein synthesis in sex-dependent cognitive performance.
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000278728 650_7 $$2Other$$alearning and memory
000278728 650_7 $$2Other$$aprotein translation
000278728 650_7 $$2Other$$aqueuosine
000278728 650_7 $$2Other$$asex bias
000278728 650_7 $$2Other$$atRNA modifications
000278728 7001_ $$00000-0003-1423-9322$$aDyckow, Julia$$b1
000278728 7001_ $$0P:(DE-He78)3b25531d07b6165b81f5fbacf640759c$$aLegrand, Carine$$b2
000278728 7001_ $$aSchott, Johanna$$b3
000278728 7001_ $$00009-0009-1463-3099$$aGuo, Wei$$b4
000278728 7001_ $$00000-0003-0266-9050$$aPerez Hernandez, Daniel$$b5
000278728 7001_ $$aHisaoka, Miharu$$b6
000278728 7001_ $$00000-0001-6682-9645$$aParlato, Rosanna$$b7
000278728 7001_ $$00000-0002-7663-1031$$aPitzer, Claudia$$b8
000278728 7001_ $$0P:(DE-He78)db41d10e17712fc21628c50a14f4d507$$avan der Hoeven, Franciscus$$b9$$udkfz
000278728 7001_ $$00000-0003-3647-8623$$aDittmar, Gunnar$$b10
000278728 7001_ $$00000-0002-0154-0928$$aHelm, Mark$$b11
000278728 7001_ $$00000-0001-9284-9834$$aStoecklin, Georg$$b12
000278728 7001_ $$00000-0001-7142-4116$$aSchirmer, Lucas$$b13
000278728 7001_ $$0P:(DE-He78)a8d53a8cdc716390a6cbacdead227143$$aLyko, Frank$$b14$$udkfz
000278728 7001_ $$0P:(DE-He78)93d163dbfed1c057437cbe97439bba99$$aTuorto, Francesca$$b15$$eLast author
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