Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Profiling of mRNA localization of nuclear-encoded mitochondrial proteins in zebrafish.

ABSTRACT: Current evidence suggests that nuclear-encoded mitochondrial proteins can be locally translated at the mitochondrial surface and co-translationally or post-translationally imported into mitochondria. mRNA localization on the mitochondrial membrane, a prerequisite for localized translation, remains uncharacterized in higher eukaryotic organisms. We employed fractionation-sequencing to profile mitochondria-associated mRNAs in zebrafish larvae. Our transcriptome-wide analysis reveals the localization of mRNAs of only 12% of the nuclear-encoded mitochondrial proteins to the mitochondrial surface, which suggests that post-translational import is the dominant mode of protein import to mitochondria. Additionally, the mRNAs which were localized to the mitochondrial membrane consisted mostly of those encoding proteins involved in mitochondrial dynamics, suggesting their site-specific translation. Finally, we show that the loss of function of the MIA pathway responsible for the post-translational import of a subclass of mitochondrial proteins, triggers mitochondrial localization of mRNAs encoding proteins that are imported to mitochondria via other pathways. Thus, our study suggests that mRNA targeting and localized translation could be relevant in higher eukaryotes to combat stress conditions affecting mitochondrial biogenesis in general.

ORGANISM(S): Danio rerio

PROVIDER: GSE160355 | GEO | 2023/10/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

A genome-scale analysis of mitochondrial-associated mRNAs in plants: upstream AUGs in 5’UTRs alter mRNA targeting

Project description:Intracellular sorting of mRNAs is an essential process to regulate gene expression and protein localization. Most of mitochondrial proteins are nuclear-encoded and imported into mitochondria, through post-translational or co-translational processes. To determine cytosolic mRNAs targeted to the mitochondrial surface, a genome-scale analysis of mRNAs associated with mitochondria has been performed in plants. As expected, many messengers encoding mitochondrial proteins were found associated with mitochondria, but numerous mRNAs encoding cytosolic proteins were also detected. This suggests multiple roles for mRNA targeting, in addition to the co-translational import of mitochondrial proteins. Moreover, correlations between mRNA targeting and function of mitochondrial proteins indicate a coordinated control of mRNAs localization within metabolic pathways. At last, upstream AUGs in 5'UTR, known to regulate translation efficiency of downstream sequences, affect mRNA targeting. A mutational approach coupled with in vivo mRNA visualization confirms this observation, and highlights the role of upstream AUGs as regulators of mRNA targeting to the mitochondrial surface.

2018-08-01 | GSE91388 | GEO

mitoCPR - a surveillance pathway that protects mitochondria in response to mitochondrial import stress

Project description:Mitochondrial functions are essential for cell viability and rely on protein import into the organelle. Various disease and stress conditions can lead to mitochondrial import defects. We find that inhibition of mitochondrial import in budding yeast activates a surveillance mechanism, mitoCPR, that is aimed at ameliorating mitochondrial import and protecting mitochondria during import stress. mitoCPR induces expression of Cis1 which associates with the mitochondrial translocase to reduce the accumulation of mitochondrial precursor proteins at the organelle surface. Clearance of precursor proteins depends on the Cis1 interacting AAA+ ATPase Msp1 and the proteasome suggesting that Cis1 facilitates degradation of un-imported proteins at the mitochondrial surface.

2018-04-20 | GSE107784 | GEO

Mitochondrially-imported RNA in Drug Discovery

Project description:The import of nuclear transcribed RNAs into mitochondria is an emerging area that presents tremendous opportunity to develop human metabolic therapeutics. However, our knowledge base is quite limited. Much remains to be discovered regarding specific RNA localization and mechanisms of import. In order to identify novel RNAs imported into mitochondria, all RNAs within the mitochondria were characterized using next generation sequencing technology. Several nuclear transcribed RNAs were found within mitochondrial RNA samples, including nuclear ribosomal RNAs, gamma satellite RNA and VL30 retroelement RNA. The presence of these RNAs within mitochondria coupled with RNA sequencing data (RNAseq) from other laboratories investigating mitochondrial RNA processing, lead us to hypothesize that nuclease treatment of mitoplasts is insufficient for removing contaminating cytoplasmic RNAs. In contrast to traditional methodology, mitochondrial import was evaluated by qRT-PCR after stepwise removal of the outer mitochondrial membrane and subsequent lysis of mitochondria. This allowed identification of RNAs lost from the mitochondria with the same kinetics as mtDNA-transcribed RNAs. This approach provided an improved evaluation of nuclear RNA enrichment within mitochondrial membranes in order to characterize nuclease protection and mitochondrial import and identify false-positive detection errors. qRT-PCR results confirmed the presence of VL30 retroelement RNA within mitochondria and question the hypothesis that the RNA component of RNase P is imported. These results illustrate a reliable approach for evaluating the presence of RNAs within mitochondria and open new avenues of investigation relating to mitochondrial RNA biology and in targeting mitochondrial based therapeutics.

2017-10-08 | GSE62170 | GEO

Targeting and Plasticity of Mitochondrial Proteins Revealed by Proximity-Specific Ribosome Profiling

Project description:Nearly all mitochondrial proteins are nuclear-encoded and are targeted to their mitochondrial destination from the cytosol. Here, we used proximity-specific ribosome profiling to comprehensively measure translation at the mitochondrial surface in yeast. The majority of inner membrane proteins were co-translationally targeted to mitochondria, reminiscent of proteins entering the endoplasmic reticulum (ER). Comparison between mitochondrial and ER localization demonstrated that the vast majority of proteins were targeted to a specific organelle. A prominent exception was the fumarate reductase Osm1, known to reside in mitochondria. We identified a conserved ER isoform of Osm1, which contributes to the oxidative protein folding capacity of the organelle. This dual localization was enabled by alternative translation initiation sites encoding distinct targeting signals. These findings highlight the exquisite in vivo specificity of organellar targeting mechanisms.

2014-11-10 | GSE61011 | GEO

Mitoprotein-induced stress launches a global transcriptional fail-safe program

Project description:Most mitochondrial proteins are synthesized as cytosolic precursor proteins before being imported into mitochondria. Cytosolic accumulation of mitochondrial precursors hazards cellular fitness and is associated with a growing number of diseases, but is not observed under physiological conditions. Individual mechanisms how cells avoid precursor accumulation outside mitochondria have recently been discovered, but their interplay and regulation have remained elusive. Here we show that cells rapidly launch a global transcriptional program to restore cellular proteostasis after induction of a “clogger” protein that reduces the number of available mitochondrial import sites. Cells upregulate the protein folding and proteolytic systems in the cytosol and downregulate both the cytosolic translation machinery and many mitochondrial metabolic enzymes, presumably to relieve the workload of the overstrained mitochondrial import system. We show that this transcriptional remodeling is a combination of a “wideband” core response regulated by the transcription factors Hsf1 and Rpn4 and a unique mitoprotein-induced downregulation of the OXPHOS components, the most abundant group of precursors. These findings not only depict the first comprehensive model of adaptations to mitochondrial import impairment, but also reveal their regulation, connecting so far isolated stress response mechanisms into a coordinated network of cellular reactions.

2019-01-12 | GSE116749 | GEO

Inter-organellar and systemic survival responses to impaired mitochondrial matrix protein import in skeletal muscle

Project description:Mitochondrial functions are largely performed by proteins imported from cytosol. Impaired protein import in mitochondria affects the maintenance of intra-mitochondrial anabolic and energy metabolic pathways. It leads to cytosolic accumulation of mistargeted proteins and activation of cellular stress responses. To explore the communication between these mechanism in mammalian system, we targeted the co-chaperone of mitochondrial Hsp70, a GrpE Like protein 1 (Grpel1), in mice. We show that loss of protein import into mitochondrial matrix results in mitochondrial dysfunction, which triggers stress responses. The total shut down of mtHSP70 function by overall knockout of Grpel1 resulted in early embryonic lethality, and tamoxifen-induced skeletal muscle-specific knockout of Grpel1 caused rapid muscular atrophy. We show here, with transcriptomics analysis, that protein-import failure in mitochondria increased cellular proteotoxic stress due to mitochondrial dysfunction. As a control mechanism, it triggered adaptive stress responses, including unfolded protein responses and integrated stress responses. Metabolic profiling of skeletal muscle-specific knockout mice revealed amino acid and TCA cycle intermediates shuttle between serum and muscle.

2022-10-04 | GSE198540 | GEO

Mammalian oocytes store mRNAs in a mitochondria-associated membraneless compartment

Project description:Fully-grown oocytes are transcriptionally silent and must stably maintain mRNAs needed for oocyte meiotic maturation and early embryonic development. However, where and how mammalian oocytes store maternal mRNAs is unclear. Here, we report that mammalian oocytes accumulate mRNAs in a mitochondria-associated ribonucleoprotein domain (MARDO). MARDO assembly around mitochondria was promoted by the RNA-binding protein ZAR1, and directed by an increase in mitochondrial membrane potential during oocyte growth. MARDO foci coalesced into hydrogel-like matrices that clustered mitochondria. Maternal mRNAs stored in the MARDO were translationally repressed. Loss of ZAR1 disrupted the MARDO, dispersed mitochondria, and caused a premature loss of MARDO-localized mRNAs. Thus, a mitochondria-associated membraneless compartment controls mitochondrial distribution and regulates maternal mRNA storage, translation and decay to ensure fertility in mammals.

2022-10-25 | PXD036974 | Pride

Endogenous TOM20 proximity labelling: a Swiss-knife for the study of mitochondrial proteins in human cells

Project description:The majority of mitochondrial proteins are encoded by the nuclear genome and must be imported into the mitochondria. There are two main paths for mitochondrial protein import: post-translational and co-translational import. Co-translational import couples the translation and the translocation of the mitochondrial proteins, alleviating the energy cost typically associated with the post-translational import relying on chaperone systems. The mitochondrial co-translational import mechanisms are still unclear with few actors identified but none have been described in mammals yet. We thus profiled the TOM20 proxisome using BioID, assuming that some of identified proteins could be molecular actors of the co-translational import in human cells. The obtained results showed a high enrichment of RNA binding proteins close to the TOM complex. However, for the few selected candidates, we could not demonstrate a role in the mitochondrial co-translational import process. Nonetheless, we were able to demonstrate a new mitochondrial localization for nuclear proteins. Besides, additional analyses revealed a negative correlation between the abundance of mitochondrial proteins and their reported half-life. This experimental approach is thus proposed to potentially characterize mitochondrial co-translational import effectors in human cells and to monitor protein entry inside mitochondria with a potential application in the prediction of mitochondrial protein half-life.

2023-07-20 | PXD038821 | Pride

FRIENDLY (FMT) is an RNA binding protein associated with cytosolic ribosomes at the mitochondrial surface

Project description:The spatial organization of protein synthesis in the eukaryotic cell is essential for maintaining the integrity of the proteome and the functioning of the cell. Translation on free polysomes or on ribosomes associated with the endoplasmic reticulum has been studied for a long time. More recent data have revealed selective translation of mRNAs in other compartments, in particular at the surface of mitochondria. Although these processes have been described in many organisms, in particular in plants, the mRNA targeting and localized translation mechanisms remain poorly understood. Here, the Arabidopsis thaliana Friendly (FMT) protein is shown to be a cytosolic RNA binding protein that associates with cytosolic ribosomes at the surface of mitochondria. As previously shown (El Zawily et al., 2014), FMT knock-out delays seedling development and causes mitochondrial clustering. The mutation also disrupts the mitochondrial proteome, and the localization of nuclear transcripts encoding mitochondrial proteins at the surface of mitochondria. These data indicate that FMT participates in the localization of mRNAs and their translation at the surface of mitochondria.

2023-02-06 | PXD035707 | Pride

Mitochondrial unfolded protein response controls matrix pre-RNA processing and translation

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data