Queuosine-tRNA promotes sex-dependent learning and memory formation by maintaining codon-biased translation elongation speed.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA749454 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15236500.fastq.gz | Fastqsanger.gz | |||
| SRR15236501.fastq.gz | Fastqsanger.gz | |||
| SRR15236502.fastq.gz | Fastqsanger.gz | |||
| SRR15236503.fastq.gz | Fastqsanger.gz | |||
| SRR15236504.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description: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 QtRNA 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 Qdependent 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.
2023-08-16 | GSE180766 | GEO
Project description: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.
| S-EPMC10548180 | biostudies-literature
Project description: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.
| S-SCDT-10_15252-EMBJ_2022112507 | biostudies-other
Project description:Post-transcriptional modification of tRNAs is critical for protein synthesis. Queuosine (Q), a 7-deaza-guanosine derivative, is present at the first position of anticodons of several tRNA species. In vertebrate tRNAs for Tyr and Asp, Q is further glycosylated with galactose and mannose to generate galactosyl-queuosine (galQ) and mannosyl-queuosine (manQ), respectively. However, the biogenesis and physiological relevance of Q-glycosylation remain poorly understood. Here, we biochemically identified two RNA glycosylases, queuosine-tRNA galactosyltransferase (QTGAL) and queuosine-tRNA mannosyltransferase (QTMAN), and successfully reconstituted galQ and manQ formation on the respective tRNAs in the presence of nucleotide diphosphate sugars. Ribosome profiling analyses of human knockout (KO) cells of QTGAL and QTMAN revealed that Q-glycosylation slowed down elongation at the cognate codons, UAC and GAC (GAU), respectively. Furthermore, protein aggregates were significantly increased in both KO cell lines, indicating that Q-glycosylation contributes to proteostasis of nascent proteins. We determined atomic structures of human cytoplasmic tRNAs for Try and Asp bound to the ribosome A-site, providing the molecular basis of codon recognition regulated by galQ and manQ. Furthermore, zebrafish qtgal and qtman KO lines displayed shortened body length, suggesting Q-glycosylation is required for post-embryonic growth in vertebrates. These findings demonstrate that Q-glycosylation modulates codon-specific translation to optimize the decoding speed in protein synthesis, thereby maintaining correct folding of nascent proteins, proteome integrity, and normal growth of vertebrates.
2023-11-21 | GSE213181 | GEO
Project description:Tgt is responsible for the queuosine (Q) modification of the guanine (G) in tRNAs with GUN anti-codon. We have previously identified tgt as being vital for growth in presence sub-lethal concentrations of aminoglycosides in Vibrio cholerae. Here we further explore the role of Q modification in translation fidelity and efficiency of codon decoding upon tobramycin exposure. We characterize the impact on codon decoding efficiency, the overall translation of the bacterial proteome, and the molecular mechanisms underlying the effects of Q modification in antibiotic stress response. Using molecular reporters, we show that Q modification impacts the efficiency of decoding at tyrosine TAT and TAC codons. Proteomics identify the anti-SoxR factor RsxA as better translated in the absence of tgt. RsxA displays a codon bias towards tyrosine TAT and its overabundance leads to decreased expression of genes belonging to SoxR oxidative stress regulon. We also identify conditions which regulate tgt expression. We propose that regulation of Q modification in response to environmental cues leads to translational reprogramming of genes bearing a biased tyrosine codon usage. In silico analysis further identifies candidate genes possibly subjected to such translational regulation, among which DNA repair factors. Such transcripts, which fit the definition of modification tunable transcripts, are plausibly central in the bacterial response to antibiotic stress.
2024-12-11 | PXD035297 | Pride
Project description:Tgt is the enzyme modifying the guanine (G) in tRNAs with GUN anticodon to queuosine (Q). tgt is required for optimal growth of Vibrio cholerae in the presence of sub-lethal aminoglycoside concentrations. We further explored here the role of the Q in the efficiency of codon decoding upon tobramycin exposure. We characterized its impact on the overall bacterial proteome, and elucidated the molecular mechanisms underlying the effects of Q modification in antibiotic translational stress response. Using molecular reporters, we showed that Q impacts the efficiency of decoding at tyrosine TAT and TAC codons. Proteomics analyses revealed that the anti-SoxR factor RsxA is better translated in the absence of tgt. RsxA displays a codon bias towards tyrosine TAT and overabundance of RsxA leads to decreased expression of genes belonging to SoxR oxidative stress regulon. We also identified conditions that regulate tgt expression. We propose that regulation of Q modification in response to environmental cues leads to translational reprogramming of genes bearing a biased tyrosine codon usage. In silico analysis further identified candidate genes possibly subject to such translational regulation, among which DNA repair factors. Such transcripts, fitting the definition of modification tunable transcripts, are plausibly central in the bacterial response to antibiotics.
2025-01-06 | GSE231087 | GEO
Project description:A snoRNA–tRNA modification network governs codon-biased cellular states
| PRJNA982754 | ENA
Project description:Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming
| PRJNA955266 | ENA
Project description:A snoRNA–tRNA modification network governs codon-biased cellular states [RMseq]
| PRJNA982109 | ENA
Project description:The dynamic balance between tRNA supply and codon usage demand is a fundamental principle in the cellular translation economy. However, the regulation and functional consequences of this balance remain unclear. Here, we use PARIS2 interactome capture, structure modeling, conservation analysis, RNA–protein interaction analysis, and modification mapping to reveal the targets of hundreds of snoRNAs, many of which were previously considered orphans. We identify a snoRNA–tRNA interaction network that is required for global tRNA modifications, including 2′-O-methylation and others. Loss of Fibrillarin, the snoRNA-guided 2′-O-methyltransferase, induces global upregulation of tRNA fragments, a large group of regulatory RNAs. In particular, the snoRNAs D97/D133 guide the 2′-O-methylation of multiple tRNAs, especially for the amino acid methionine (Met), a protein-intrinsic antioxidant. Loss of D97/D133 snoRNAs in human HEK293 cells reduced target tRNA levels and induced codon adaptation of the transcriptome and translatome. Both D97/D133 single and double knockouts in HEK293 cells suppress Met-enriched proliferation-related gene expression programs, including, translation, splicing, and mitochondrial energy metabolism, and promote Met-depleted programs related to development, differentiation, and morphogenesis. In a mouse embryonic stem cell model of development, knockdown and knockout of D97/D133 promote differentiation to mesoderm and endoderm fates, such as cardiomyocytes, without compromising pluripotency, consistent with the enhanced development-related gene expression programs in human cells. This work solves a decade-old mystery about orphan snoRNAs and reveals a function of snoRNAs in controlling the codon-biased dichotomous cellular states of proliferation and development.
2023-09-21 | GSE234689 | GEO