Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
DUX4 is a transcription factor whose misexpression in skeletal muscle causes facioscapulohumeral muscular dystrophy (FSHD). DUX4's transcriptional activity has been extensively characterized, but the DUX4-induced proteome remains undescribed. Here, we report concurrent measurement of RNA and protein levels in DUX4-expressing cells via RNA-seq and quantitative mass spectrometry. DUX4 transcriptional targets were robustly translated, confirming the likely clinical relevance of proposed FSHD biomarkers. However, a multitude of mRNAs and proteins exhibited discordant expression changes upon DUX4 expression. Our dataset revealed unexpected proteomic, but not transcriptomic, dysregulation of diverse molecular pathways, including Golgi apparatus fragmentation, as well as extensive post-transcriptional buffering of stress-response genes. Key components of RNA degradation machineries, including UPF1, UPF3B, and XRN1, exhibited suppressed protein, but not mRNA, levels, explaining the build-up of aberrant RNAs that characterizes DUX4-expressing cells. Our results provide a resource for the FSHD community and illustrate the importance of post-transcriptional processes in DUX4-induced pathology.
Pubmed ID: 30644821
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Collection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.
View all literature mentionsWeb based gene set analysis toolkit designed for functional genomic, proteomic, and large-scale genetic studies from which large number of gene lists (e.g. differentially expressed gene sets, co-expressed gene sets etc) are continuously generated. WebGestalt incorporates information from different public resources and provides a way for biologists to make sense out of gene lists. This version of WebGestalt supports eight organisms, including human, mouse, rat, worm, fly, yeast, dog, and zebrafish.
View all literature mentionsA tool for identifying and visualizing enriched GO terms in ranked lists of genes. It can be run in one of two modes: * Searching for enriched GO terms that appear densely at the top of a ranked list of genes or * Searching for enriched GO terms in a target list of genes compared to a background list of genes.
View all literature mentionsPercolator post-processes the results of a shotgun proteomics database search program, re-ranking peptide-spectrum matches so that the top of the list is enriched for correct matches. Shotgun proteomics uses liquid chromatography-tandem mass spectrometry to identify proteins in complex biological samples. We describe an algorithm, called Percolator, for improving the rate of peptide identifications from a collection of tandem mass spectra. Percolator uses semi-supervised machine learning to discriminate between correct and decoy spectrum identifications, correctly assigning peptides to 17% more spectra from a tryptic dataset and up to 77% more spectra from non-tryptic digests, relative to a fully supervised approach. The yeast-01 data is available in tab delimetered format. The SEQUEST parameter file and target database for the yeast and worm data are also available.
View all literature mentions