YBEY is an essential biogenesis factor for mitochondrial ribosomes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA556886 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9846862_1.fastq.gz | Fastqsanger.gz | |||
| SRR9846862_2.fastq.gz | Fastqsanger.gz | |||
| SRR9846863_1.fastq.gz | Fastqsanger.gz | |||
| SRR9846863_2.fastq.gz | Fastqsanger.gz | |||
| SRR9846864_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Ribosome biogenesis relies on a number of specific factors. Some of them are remarkably conserved, suggesting that they play essential roles even in distant evolutionary contexts. This is namely the case for the UPF0054 protein YBEY found in all bacteria, but also in many Eukarya. Proposed to act as an endoribonuclease processing the 3’ end of 16S rRNA, YBEY is critically required for translation in model bacteria and plant chloroplasts. However, ribosomal RNA processing pathways are poorly conserved between distant phyla, suggesting that YBEY may have another important function in ribosome biogenesis. We studied the human YBEY homologue and found that it localises in mitochondria. The human mitochondrial rRNAs are flanked by tRNA genes and thereby processed by mitochondrial RNase P and RNase Z, making other ribonucleases superfluous. Yet, CRISPR-mediated knockout of the YBEY gene resulted in a decrease of the mitochondrial small ribosomal subunits (SSU), abolished translation in the organelles and, as a result, led to the inability of the knockout cells to respire. Mapping the ends of the mitochondrial rRNAs revealed no processing defects. Similarly, although human YBEY did show robust RNase activity in vitro and in vivo, mutations in key catalytic residues did not abolish its ability to complement the knockout phenotypes. The analysis of the mitoribosomes identified a distinct set of SSU proteins, mostly located in the head and the platform, to be significantly depleted in the absence of YBEY, including uS11m, required for translation initiation. Importantly, uS11m was the only SSU protein found to directly interact with YBEY in vitro, in vivo and in situ, and forming a stable stoichiometric complex with YBEY. The sum of our data supports the model where YBEY functions primarily as an essential ribosome biogenesis factor by recruiting uS11m in order to complete the assembly of translationally active SSUs.
2020-02-26 | GSE134960 | GEO
Project description:Ribosome biogenesis is a key cellular process involving numerous protein factors, some of which are deeply conserved. This is namely the case of the bacterial endoribonuclease YbeY, whose loss is associated with ribosomal abnormalities, profound changes in gene expression, altered metabolism and death. Surprisingly, YbeY is also widespread among eukaryotes. Here we provide an in-depth characterisation of the human YBEY homologue localising in mitochondria. We show that YBEY loss results in a severe mitochondrial phenotype and complete inability of mitochondria to translate proteins and, consequently, perform oxidative phosphorylation. Through interactions with the important disease protein p32 and other factors, YBEY functions to recruit the mitoribosomal protein uS11m to the nascent small subunit in order to complete the assembly of initiation-competent ribosomal particles. This likely conserved mechanism shows striking similarities with final stages of the cytosolic ribosome biogenesis and may provide an important late checkpoint before the mitoribosome engages in translation.
2021-04-29 | PXD014959 | Pride
Project description:The aim was to evaluate the protein composition of human mitoribosomes in YBEY knockout cells. We compared the parental cell line HEK293T-REx with the YBEY knockout cells HEK293T-RExΔYBEY.
2020-03-02 | PXD015310 | Pride
Project description:Ribosome biogenesis requires numerous trans-acting factors, some of which are deeply conserved. In Bacteria, the endoribonuclease YbeY is believed to be involved in 16S rRNA 3'-end processing and its loss was associated with ribosomal abnormalities. In Eukarya, YBEY appears to generally localize to mitochondria (or chloroplasts). Here we show that the deletion of human YBEY results in a severe respiratory deficiency and morphologically abnormal mitochondria as an apparent consequence of impaired mitochondrial translation. Reduced stability of 12S rRNA and the deficiency of several proteins of the small ribosomal subunit in YBEY knockout cells pointed towards a defect in mitochondrial ribosome biogenesis. The specific interaction of mitoribosomal protein uS11m with YBEY suggests that the latter helps to properly incorporate uS11m into the nascent small subunit in its late assembly stage. This scenario shows similarities with final stages of cytosolic ribosome biogenesis, and may represent a late checkpoint before the mitoribosome engages in translation.
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Project description:Caloric restriction (CR) without malnutrition appears to mitigate many detrimental effects of aging, in particular the age-related decline in skeletal muscle mitochondrial function. Although the mechanisms responsible for this protective effect remain unclear, CR is commonly believed to increase mitochondrial biogenesis; a concept that is now demanding closer scrutiny. Here we show that lifelong CR in mice prevents age-related loss of mitochondrial function, measured in isolated mitochondria and permeabilized muscle fibers. We find that these beneficial effects of CR occur without increasing mitochondrial abundance. Furthermore, whole-genome expression profiling and large-scale proteomic surveys revealed expression patterns inconsistent with increased mitochondrial biogenesis. These observations, combined with lower protein synthesis rates support an alternative hypothesis that CR preserves mitochondrial function not by increasing mitochondrial biogenesis, but rather by decreasing mitochondrial oxidant emission, increasing antioxidant scavenging, thereby minimizing oxidative damage to cellular components. Cross-sectional comparison of skeletal muscle from young (8mo), old (24mo) and old caloric restricted mice, obtained from the colony maintained on behalf of the National Institute on Aging.
2013-01-01 | E-GEOD-36285 | biostudies-arrayexpress
Project description:The antibiotics chloramphenicol (CHL) and oxazolidinones including linezolid (LZD) are known to inhibit mitochondrial translation. This can result in serious, potentially deadly, side effects when used therapeutically. Although the mechanism by which CHL and LZD inhibit bacterial ribosomes has been elucidated in detail, their mechanism of action against mitochondrial ribosomes has yet to be explored. CHL and oxazolidinones bind to the ribosomal peptidyl transfer center (PTC) of the bacterial ribosome and prevent incorporation of incoming amino acids under specific sequence contexts, causing ribosomes to stall only at certain sequences. Through mitoribosome profiling, we show that inhibition of mitochondrial ribosomes is similarly context-specific – CHL and LZD lead to mitoribosome stalling primarily when there is an alanine, serine, or threonine in the penultimate position of the nascent peptide chain. Our findings could help inform the rational development of future, less mitotoxic, antibiotics, which are critically needed in the current era of increasing antimicrobial resistance.
2024-10-01 | GSE273206 | GEO
Project description:Mitochondrial proteins are replete with phosphorylation; however, the origin, abundance, and functional relevance of these modifications are largely unclear. Nonetheless, mitochondria possess multiple resident phosphatases, suggesting that protein dephosphorylation may be broadly important for mitochondrial activities. To explore this, we deleted the poorly characterized matrix phosphatase Pptc7 from mice using CRISPR-Cas9 technology. Strikingly, Pptc7-/- mice exhibited marked hypoketotic hypoglycemia, elevated acylcarnitines, and lactic acidosis, and died soon after birth. Pptc7-/- tissues had significantly diminished mitochondrial size and protein content despite normal transcript levels, but consistently elevated phosphorylation on select mitochondrial proteins. These putative Pptc7 substrates include the protein translocase complex subunit Timm50, whose phosphorylation reduced import activity. We further find that phosphorylation in or near the mitochondrial targeting sequences of multiple proteins can disrupt their import rates and matrix processing. Overall, our data define Pptc7 as a protein phosphatase essential for proper mitochondrial function and biogenesis during the extrauterine transition. Natalie M Niemi, Gary M Wilson, Katherine A Overmyer, F.-Nora Vogtle, Danielle C Lohman, Kathryn L Schueler, Alan D Attie, Chris Meisinger, Joshua J Coon, David J Pagliarini. (2018) “Pptc7 is an essential phosphatase for promoting mammalian mitochondrial metabolism and biogenesis.” biorx: https://doi.org/10.1101/426247
2019-05-29 | PXD012743 | Pride
Project description:Caloric restriction (CR) without malnutrition appears to mitigate many detrimental effects of aging, in particular the age-related decline in skeletal muscle mitochondrial function. Although the mechanisms responsible for this protective effect remain unclear, CR is commonly believed to increase mitochondrial biogenesis; a concept that is now demanding closer scrutiny. Here we show that lifelong CR in mice prevents age-related loss of mitochondrial function, measured in isolated mitochondria and permeabilized muscle fibers. We find that these beneficial effects of CR occur without increasing mitochondrial abundance. Furthermore, whole-genome expression profiling and large-scale proteomic surveys revealed expression patterns inconsistent with increased mitochondrial biogenesis. These observations, combined with lower protein synthesis rates support an alternative hypothesis that CR preserves mitochondrial function not by increasing mitochondrial biogenesis, but rather by decreasing mitochondrial oxidant emission, increasing antioxidant scavenging, thereby minimizing oxidative damage to cellular components.
2013-01-01 | GSE36285 | GEO
Project description:LARP7 controls the SIRT1 activity and homeostasis, which is essential for mitochondrial biogenesis, energy production and cardiac function. The deprivation of LARP7 resulted from the activation ATM pathway attenuates the mitochondrial function and biogenesis and leads to the cardiomyopathy and heart failure. Method: Heart morphology and functions were assessed by gross anatomy, serial echocardiography and histology on sections; Mitochondrial morphology and activity were evaluated by TEM and seahorse assays. The therapeutic potential of LARP7 in heart failure was evaluated in mouse myocardial infarction model either with AAV9 infection or pharmacological inhibitor.
2020-08-14 | GSE155898 | GEO
Project description:Parkin, an E3 ubiquitin ligase, plays an essential role in mitochondrial quality control. However, the mechanisms by which Parkin connects mitochondrial homeostasis to cellular metabolism in adipose tissue remain unclear. Here, we demonstrate that Park2 gene (encodes Parkin) deletion specifically from adipose tissue protects mice against high-fat diet and aging-induced obesity. Despite a mild reduction in mitophagy, mitochondrial DNA (mtDNA) content and mitochondrial function are significantly increased in Park2 deficient white adipocytes. Moreover, Park2 gene deletion robustly elevates mitochondrial biogenesis by increasing Pgc1α protein stability through mitochondrial superoxide-activated Nqo1. Both in vitro and in vivo studies show that Nqo1 overexpression elevates Pgc1α protein level and mtDNA content and enhances mitochondrial activity in mouse and human adipocytes. Taken together, our findings indicate that Parkin regulates mitochondrial homeostasis by balancing mitophagy and Pgc1α-mediated mitochondrial biogenesis in white adipocytes, suggesting a potential therapeutic target in adipocytes to combat obesity and obesity-associated disorders.
2022-09-29 | GSE207496 | GEO