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Strict regulation of epithelial cells is crucial for maintaining intestinal barrier integrity and preventing intestinal diseases. While transcriptional regulation is well recognized as vital in this process, translational regulation is equally important. SETD2, a methyltransferase, is involved in transcriptional regulation to maintain intestinal epithelial barrier function. However, its role in translation remains largely unexplored. Here, we found SETD2 deficiency leads to the downregulation of ribosome biogenesis progress coupled with transcriptome-proteome discordance. Further ribosome profiling sequencing analyses showed reduced translational efficiency of cell adhesion and junction signatures in impaired intestinal epithelial barrier. Mechanistically, SETD2 ablation causes dysregulation and recruitment disorders of ribosome biogenesis factors, impairing the composition and distribution of ribosomal proteins. This disruption of ribosome biogenesis and homeostasis results in translational disorder of barrier maintenance genes, thereby compromising the intestinal barrier. Collectively, our findings unveil a previously unappreciated role of ribosome biogenesis and translational regulation in safeguarding intestinal epithelial barrier, and disclose a previously undiscovered role of SETD2 in modulating ribosome homeostasis.
Pubmed ID: 41486761
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Web tool to search, sort, analyze, visualize and download data of interest. Along with providing details of the ontologies, gene products and annotations, features a BLAST search, Term Enrichment and GO Slimmer tools, the GO Online SQL Environment and a user help guide.Used at the Gene Ontology (GO) website to access the data provided by the GO Consortium. Developed and maintained by the GO Consortium.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsHigh quality ribosomal RNA databases providing comprehensive, quality checked and regularly updated datasets of aligned small (16S/18S, SSU) and large subunit (23S/28S, LSU) ribosomal RNA (rRNA) sequences for all three domains of life (Bacteria, Archaea and Eukarya). Supplementary services include a rRNA gene aligner, online tools for probe and primer evaluation and optimized browsing, searching and downloading on the website. The extensively curated SILVA taxonomy and the new non-redundant SILVA datasets provide an ideal reference for high-throughput classification of data from next-generation sequencing approaches. Alignment tool, SINA, is available for download as well as available for use online.
View all literature mentionsPublic database with millions of high-resolution images showing the spatial distribution of proteins in different normal human tissues and cancer types, as well as different human cell lines. The data is released together with application-specific validation performed for each antibody, including immunohistochemisty, Western blot analysis and, for a large fraction, a protein array assay and immunofluorescent based confocal microscopy. The database has been developed in a gene-centric manner with the inclusion of all human genes predicted from genome efforts. Search functionalities allow for complex queries regarding protein expression profiles, protein classes and chromosome location. Antibodies included have been analyzed using a standardized protocol in a single attempt without further efforts to optimize the procedure and therefore it cannot be excluded that certain observed binding properties are due to technical rather than biological reasons and that further optimization could result in a different outcome. Submission of antibodies: The Swedish Human Proteome Atlas (HPA) program, invites submission of antibodies from both academic and commercial sources to be included in the human protein atlas. All antibodies will be validated by the HPA-program by a standard procedure and antibodies that are accepted will be use in the tissue- profiling program to generate high-resolution immunohistochemistry images representing a wide spectrum of normal tissues and cancer types.
View all literature mentionsThis genomic tRNA database contains tRNA gene predictions made by the program tRNAscan-SE (Lowe & Eddy, Nucl Acids Res 25: 955-964, 1997) on complete or nearly complete genomes. Unless otherwise noted, all annotation is automated, and has not been inspected for agreement with published literature. Transfer RNAs (tRNAs) represent the single largest, best-understood class of non-protein coding RNA genes found in all living organisms. By far, the major source of new tRNAs is computational identification of genes within newly sequenced genomes. To organize the rapidly growing collection and enable systematic analyses, we created the Genomic tRNA Database (GtRNAdb). The web resource provides overview statistics of tRNA genes within each analyzed genome, including information by isotype and genetic locus, easily downloadable primary sequences, graphical secondary structures and multiple sequence alignments. Direct links for each gene to UCSC eukaryotic and microbial genome browsers provide graphical display of tRNA genes in the context of all other local genetic information. The database can be searched by primary sequence similarity, tRNA characteristics or phylogenetic group. Inevitably with automated sequence analysis, we find exceptions to general identification rules, isoacceptor type predictions (esp. due to variable post-transcriptional anticodon modification), and questionable tRNA identifications (due to pseudogenes, SINES, or other tRNA-derived elements). We attempt to document all cases we come across, and welcome feedback on new or unrecognized discrepancies.
View all literature mentionsA read summarization program, which counts mapped reads for the genomic features such as genes and exons.
View all literature mentionsHuman and mouse genome annotation project which aims to identify all gene features in the human genome using computational analysis, manual annotation, and experimental validation.
View all literature mentionsGraph-based alignment of next generation sequencing reads to a population of genomes.
View all literature mentionsSoftware R package for statistical analysis and visualization of functional profiles for genes and gene clusters.
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