Backgrounds And Aims: Transfer RNA (tRNA) is the most extensively modified RNA in cells. Queuosine modification is a fundamental process for ensuring the fidelity and efficiency of translation from RNA to protein. In eukaryotes, Queuosine tRNA (Q-tRNA) modification relies on the intestinal microbial product queuine. However, the roles and potential mechanisms of Q-containing tRNA (Q-tRNA) modifications in inflammatory bowel disease (IBD) are unknown.
Methods: We explored the Q-tRNA modifications and expression of QTRT1 (queuine tRNA-ribosyltransferase 1) in patients with IBD by investigating human biopsies and reanalyzing datasets. We used colitis models, QTRT1 knockout mice, organoids, and cultured cells to investigate the molecular mechanisms of Q-tRNA modifications in intestinal inflammation.
Results: QTRT1 expression was significantly downregulated in ulcerative colitis and Crohn's disease patients. The 4 Q-tRNA-related tRNA synthetases (asparaginyl-, aspartyl-, histidyl-, and tyrosyl-tRNA synthetase) were decreased in IBD patients. This reduction was further confirmed in a dextran sulfate sodium-induced colitis model and interleukin-10-deficient mice. Reduced QTRT1 was significantly correlated with cell proliferation and intestinal junctions, including downregulation of β-catenin and claudin-5 and the upregulation of claudin-2. These alterations were confirmed in vitro by deleting the QTRT1 gene from cells and in vivo using QTRT1 knockout mice. Queuine treatment significantly enhanced cell proliferation and junction activity in cell lines and organoids. Queuine treatment also reduced inflammation in epithelial cells. Moreover, altered QTRT1-related metabolites were found in human IBD.
Conclusions: tRNA modifications play an unexplored novel role in the pathogenesis of intestinal inflammation by altering epithelial proliferation and junction formation. Further investigation of the role of tRNA modifications will uncover novel molecular mechanisms for the prevention and treatment of IBD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140797 | PMC |
| http://dx.doi.org/10.1016/j.jcmgh.2023.02.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mechanism of Catalysis and Substrate Binding of Epoxyqueuosine Reductase in the Biosynthetic Pathway to Queuosine-Modified tRNA.
Biochemistry
December 2024
Department of Chemistry, University of Florida, Gainesville, Florida 32611, United States.
Post-transcriptional modifications at the anticodon stem-loop of tRNAs are key to the translation function. Metabolic pathways to these modifications often incorporate complex enzymology. A notable example is the hypermodified nucleoside, queuosine, found at the wobble position of Asn, Asp, His, and Tyr encoding tRNAs.
View Article and Find Full Text PDFQueuosine biosynthetic enzyme, QueE moonlights as a cell division regulator.
PLoS Genet
May 2024
Waksman Institute of Microbiology and Department of Genetics, Rutgers University, Piscataway New Jersey, United States of America.
In many organisms, stress responses to adverse environments can trigger secondary functions of certain proteins by altering protein levels, localization, activity, or interaction partners. Escherichia coli cells respond to the presence of specific cationic antimicrobial peptides by strongly activating the PhoQ/PhoP two-component signaling system, which regulates genes important for growth under this stress. As part of this pathway, a biosynthetic enzyme called QueE, which catalyzes a step in the formation of queuosine (Q) tRNA modification is upregulated.
View Article and Find Full Text PDFIn many organisms, stress responses to adverse environments can trigger secondary functions of certain proteins by altering protein levels, localization, activity, or interaction partners. Escherichia coli cells respond to the presence of specific cationic antimicrobial peptides by strongly activating the PhoQ/PhoP two-component signaling system, which regulates genes important for growth under this stress. As part of this pathway, a biosynthetic enzyme called QueE, which catalyzes a step in the formation of queuosine (Q) tRNA modification is upregulated.
View Article and Find Full Text PDFQueuosine-tRNA promotes sex-dependent learning and memory formation by maintaining codon-biased translation elongation speed.
EMBO J
October 2023
Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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.
View Article and Find Full Text PDFDisruption to tRNA Modification by Queuine Contributes to Inflammatory Bowel Disease.
Cell Mol Gastroenterol Hepatol
May 2023
Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois Chicago, Chicago, Illinois; UIC Cancer Center, Department of Medicine, University of Illinois Chicago, Chicago, Illinois; Department of Microbiology and Immunology, University of Illinois Chicago, Chicago, Illinois; Jesse Brown VA Medical Center Chicago, Chicago, Illinois. Electronic address:
Backgrounds And Aims: Transfer RNA (tRNA) is the most extensively modified RNA in cells. Queuosine modification is a fundamental process for ensuring the fidelity and efficiency of translation from RNA to protein. In eukaryotes, Queuosine tRNA (Q-tRNA) modification relies on the intestinal microbial product queuine.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!