Similar Datasets
Project description:The FASTK family proteins are emerging key post-transcriptional regulators in mitochondrial gene expression. In attempts to uncover their molecular functions, we carried out BioID experiments to identify proteins interacting with FASTKD4 and FASTKD5. Our data suggest that both proteins have similar protein interactome profiles, highlighting their roles in mitochondrial RNA processing.
2021-11-02 | PXD020993 | Pride
Project description:The FASTK family proteins are master regulators in mitochondrial RNA processing
| PRJNA658336 | ENA
Project description:Canonical RNA processing in mammalian mitochondria necessitates that tRNAs are recognised by nucleases to release flanking transcripts. However, not all mitochondrial transcripts are punctuated by tRNAs, and the mechanism and factors involved in their processing has remained unsolved. Here, we demonstrate that phosphatase activity of the carbon catabolite repressor 4 domain containing family member ANGEL2 is required for the hydrolysis of 3′ phosphates, resulting from non-canonical processing. Interaction studies in Drosophila further identify that members of the FAST kinase domain containing protein family are involved in the formation of these 3′ phosphates. Our results therefore resolve the mechanism of RNA processing in metazoan mitochondria, by defining the outstanding non-canonical processing mechanism.
2022-09-04 | GSE189750 | GEO
Project description:In animals the organization of the compact mitochondrial genome and lack of introns have necessitated a unique mechanism for RNA processing. To date the regulation of mitochondrial RNA processing and its importance for ribosome biogenesis and energy metabolism are not clear. To understand the in vivo role of the endoribonuclease component of the RNase P complex, MRPP3, we created conditional knockout mice. Here we show that MRPP3 is essential for life, and heart and skeletal muscle-specific knockout leads to a cardiomyopathy early in life, indicating that it is the only RNase P enzyme in mitochondria. We show that RNA processing is required for the biogenesis of the respiratory chain and mitochondrial function. Transcriptome-wide parallel analyses of RNA ends (PARE) and RNA-Seq enabled us to identify the in vivo cleavage sites of RNase P. Cleavage of the 5â² tRNA ends precedes 3â² end processing in vivo and is required for the correct biogenesis of the mitochondrial ribosomal subunits and mitoribosomal proteins that are differentially stabilized or degraded in the absence of mature rRNAs. Finally we identify that large mitoribosomal proteins can form a subcomplex on a precursor mt-RNA containing the 16S rRNA indicating that mitoribosomal biogenesis proceeds co-transcriptionally. Taken together our data show that RNA processing links transcription to translation via assembly of the mitoribosome. Total RNA was isolated from heart tissue from 11 week old control (Mrpp3loxP/loxP) and Mrpp3 knockout mice (Mrpp3loxP/loxP, +/Ckmm), TruSeq libraries produced in triplicate, sequenced and analysed for differential expression. Mitochondrial RNA was isolated from heart tissue from 11 week old control (Mrpp3loxP/loxP) and Mrpp3 knockout mice (Mrpp3loxP/loxP, +/Ckmm), PARE libraries produced in triplicate and sequenced for analysis of mitochondrial RNA processing.
2016-08-04 | E-GEOD-83471 | biostudies-arrayexpress
Project description:The expression of mitochondrially-encoded genes requires the efficient processing of long precursor RNAs at the 5´ and 3´ ends of tRNAs, a process which, when disrupted, results in disease. Two such mutations reside within mt-tRNALeu(UUR); a m.3243A>G transition, which is the most common cause of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), and m.3302A>G which often causes mitochondrial myopathy (MM). We used parallel analysis of RNA ends (PARE) that captures the 5´ terminal end of 5´-monophosphorylated mitochondrial RNAs to compare the effects of the m.3243A>G and m.3302A>G mutations on mitochondrial tRNA processing. We confirmed previously identified RNA processing defects, identified common internal cleavage sites and new sites unique to the m.3243A>G mutants that do not correspond to transcript ends. These sites occur in regions of predicted RNA secondary structure, or are in close proximity to such regions, and may identify regions of importance to the processing of mtRNAs.
2017-03-23 | GSE85549 | 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. 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:Mitochondrial RNA processing in absence of tRNA punctuations in octocorals
| PRJEB18762 | ENA
Project description:Angel2 phosphatase activity is required for non-canonical mitochondrial RNA processing in metazoa
| PRJNA784409 | ENA
Project description:Canonical RNA processing in mammalian mitochondria is defined by tRNAs acting as recognition sites for nucleases to release flanking transcripts. The relevant factors, their structures, and mechanism are well described, but not all mitochondrial transcripts are punctuated by tRNAs, and their mode of processing has remained unsolved. Using Drosophila and mouse models, we demonstrate that non-canonical processing results in the formation of 3′ phosphates, and that phosphatase activity by the carbon catabolite repressor 4 domain-containing family member ANGEL2 is required for their hydrolysis. Furthermore, our data suggest that members of the FAST kinase domain-containing protein family are responsible for these 3′ phosphates. Our results therefore resolve the mechanism of non-canonical RNA processing in metazoan mitochondria, by defining the role of ANGEL2.
2022-09-01 | PXD033394 | Pride