Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA304150 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mitochondrial unfolded protein response controls matrix pre-RNA processing and translation
| PRJNA304147 | ENA
Project description:Mitochondrial unfolded protein response controls matrix pre-RNA processing and translation
| PRJNA302895 | ENA
Project description:The mitochondrial matrix is unique in that it must integrate folding and assembly of proteins derived from nuclear and mitochondrial genomes. In C. elegans, the mitochondrial unfolded protein response (UPRmt) senses matrix protein misfolding and induces a program of nuclear gene expression, including mitochondrial chaperonins, to promote mitochondrial proteostasis. While misfolded mitochondrial matrix-localized ornithine trans-carbamylase (OTC) induces chaperonin expression, our understanding of mammalian UPRmt is rudimentary, reflecting a lack of acute triggers for UPRmt activation. This limitation has prevented analysis of the cellular responses to matrix protein misfolding and the effects of UPRmt on mitochondrial translation to control protein folding loads. Here, we combine pharmacological inhibitors of matrix-localized HSP90/TRAP1 or LON protease, which promote chaperonin expression, with global transcriptional and proteomic analysis to reveal an extensive and acute response of human cells to UPRmt. This response involved widespread induction of nuclear genes, including matrix-localized proteins involved in folding, pre-RNA processing and translation. Functional studies revealed rapid but reversible translation inhibition in mitochondria occurring concurrently with defects in pre-RNA processing due to transcriptional repression and LON-dependent turnover of the mitochondrial pre-RNA processing nuclease MRPP3. This study reveals that acute mitochondrial protein folding stress activates both increased chaperone availability within the matrix and reduced matrix-localized protein synthesis through translational inhibition, and provides a framework for further dissection of mammalian UPRmt. triplicate experiment of 3 conditions (untreated, GTPP treatment, CDDO treatment)
2016-06-28 | E-GEOD-75247 | biostudies-arrayexpress
Project description:The mitochondrial matrix is unique in that it must integrate folding and assembly of proteins derived from nuclear and mitochondrial genomes. In C. elegans, the mitochondrial unfolded protein response (UPRmt) senses matrix protein misfolding and induces a program of nuclear gene expression, including mitochondrial chaperonins, to promote mitochondrial proteostasis. While misfolded mitochondrial matrix-localized ornithine trans-carbamylase (OTC) induces chaperonin expression, our understanding of mammalian UPRmt is rudimentary, reflecting a lack of acute triggers for UPRmt activation. This limitation has prevented analysis of the cellular responses to matrix protein misfolding and the effects of UPRmt on mitochondrial translation to control protein folding loads. Here, we combine pharmacological inhibitors of matrix-localized HSP90/TRAP1 or LON protease, which promote chaperonin expression, with global transcriptional and proteomic analysis to reveal an extensive and acute response of human cells to UPRmt. This response involved widespread induction of nuclear genes, including matrix-localized proteins involved in folding, pre-RNA processing and translation. Functional studies revealed rapid but reversible translation inhibition in mitochondria occurring concurrently with defects in pre-RNA processing due to transcriptional repression and LON-dependent turnover of the mitochondrial pre-RNA processing nuclease MRPP3. This study reveals that acute mitochondrial protein folding stress activates both increased chaperone availability within the matrix and reduced matrix-localized protein synthesis through translational inhibition, and provides a framework for further dissection of mammalian UPRmt. triplicate experiment of 2 conditions (untreated, GTPP treatment)
2016-06-28 | E-GEOD-75410 | biostudies-arrayexpress
Project description:The mitochondrial matrix is unique in that it must integrate folding and assembly of proteins derived from nuclear and mitochondrial genomes. In C. elegans, the mitochondrial unfolded protein response (UPRmt) senses matrix protein misfolding and induces a program of nuclear gene expression, including mitochondrial chaperonins, to promote mitochondrial proteostasis. While misfolded mitochondrial matrix-localized ornithine trans-carbamylase (OTC) induces chaperonin expression, our understanding of mammalian UPRmt is rudimentary, reflecting a lack of acute triggers for UPRmt activation. This limitation has prevented analysis of the cellular responses to matrix protein misfolding and the effects of UPRmt on mitochondrial translation to control protein folding loads. Here, we combine pharmacological inhibitors of matrix-localized HSP90/TRAP1 or LON protease, which promote chaperonin expression, with global transcriptional and proteomic analysis to reveal an extensive and acute response of human cells to UPRmt. This response involved widespread induction of nuclear genes, including matrix-localized proteins involved in folding, pre-RNA processing and translation. Functional studies revealed rapid but reversible translation inhibition in mitochondria occurring concurrently with defects in pre-RNA processing due to transcriptional repression and LON-dependent turnover of the mitochondrial pre-RNA processing nuclease MRPP3. This study reveals that acute mitochondrial protein folding stress activates both increased chaperone availability within the matrix and reduced matrix-localized protein synthesis through translational inhibition, and provides a framework for further dissection of mammalian UPRmt.
2016-06-28 | GSE75410 | GEO
Project description:The mitochondrial matrix is unique in that it must integrate folding and assembly of proteins derived from nuclear and mitochondrial genomes. In C. elegans, the mitochondrial unfolded protein response (UPRmt) senses matrix protein misfolding and induces a program of nuclear gene expression, including mitochondrial chaperonins, to promote mitochondrial proteostasis. While misfolded mitochondrial matrix-localized ornithine trans-carbamylase (OTC) induces chaperonin expression, our understanding of mammalian UPRmt is rudimentary, reflecting a lack of acute triggers for UPRmt activation. This limitation has prevented analysis of the cellular responses to matrix protein misfolding and the effects of UPRmt on mitochondrial translation to control protein folding loads. Here, we combine pharmacological inhibitors of matrix-localized HSP90/TRAP1 or LON protease, which promote chaperonin expression, with global transcriptional and proteomic analysis to reveal an extensive and acute response of human cells to UPRmt. This response involved widespread induction of nuclear genes, including matrix-localized proteins involved in folding, pre-RNA processing and translation. Functional studies revealed rapid but reversible translation inhibition in mitochondria occurring concurrently with defects in pre-RNA processing due to transcriptional repression and LON-dependent turnover of the mitochondrial pre-RNA processing nuclease MRPP3. This study reveals that acute mitochondrial protein folding stress activates both increased chaperone availability within the matrix and reduced matrix-localized protein synthesis through translational inhibition, and provides a framework for further dissection of mammalian UPRmt.
2016-06-28 | GSE75247 | GEO
Project description:We analyzed the gene expression changes that result from mitochondria overloaded by unfolded proteins in skeletal muscles. Mitochondrial-retained mutant ornithine transcarbamylase (ΔOTC) is a known protein degraded by LONP1 and an established model for studying mitochondrial proteostasis imbalance. We generated transgenic mice overexpressing ΔOTC specifically in skeletal muscle using the muscle creatine kinase promoter (MCK-ΔOTC). Transcriptome analysis was performed by whole-genome gene expression profiling experiments in muscles from the MCK-ΔOTC mice and NTG littermate controls. The comparative mRNA profiling strategy revealed extensive genomic reprogramming in MCK-ΔOTC muscles, with 1051 genes up- and 519 genes down-regulated (1.5-fold change and p<0.05), respectively. GO analysis of the regulated genes in MCK-ΔOTC muscles revealed significant enrichment in unfolded protein response as well as RNA processing process. These data suggest that mitochondria overloaded by ΔOTC unfolded proteins induce extensive genomic reprogramming in skeletal muscle
2022-07-28 | GSE192991 | GEO
Project description:The Cytoplasmic Polyadenylation Element Binding (CPEB)-family of RNA-binding proteins regulates pre-mRNA processing and translation of CPE-containing mRNAs in early embryonic development and synaptic activity. However, the specific functions of each CPEB in the adult organism are poorly understood. Here we show that CPEB4 is required to suppress high fat diet- and aging-induced endoplasmic reticulum (ER) stress, and its subsequent hepatic steatosis. Stress-activated expression of CPEB4 in the liver is controlled through a double layer of regulation. First, Cpeb4 is transcriptionally regulated by the circadian clock and then, its mRNA translation is regulated by the Unfolded Protein Response (UPR) through the upstream Open Reading Frames (uORFs) present in its 5’ UTR. Thus, CPEB4 is synthesized only upon ER-stress but the amplitude of the induction is circadian. In turn, CPEB4 activates a second wave of UPR-translation required to maintain ER and mitochondrial homeostasis. Our results suggest that combined transcriptional and translational regulation of CPEB4 generates a “circadian mediator”, which
coordinates the hepatic UPR activity with periods of high ER protein-folding demand preventing non-alcoholic fatty liver disease (NAFLD).
2017-01-16 | GSE81876 | GEO