Import of tRNAs and aminoacyl-tRNA synthetases into mitochondria.
TL;DR: All mitochondrial aminoacyl-tRNA synthetases and many tRNAs are imported from the cytosol into the mitochondria in eukaryotic cells and their origin and their import into the organelle have been studied in evolutionary distinct organisms.
Abstract: During evolution, most of the bacterial genes from the ancestral endosymbiotic α-proteobacteria at the origin of mitochondria have been either lost or transferred to the nuclear genome. A crucial evolutionary step was the establishment of macromolecule import systems to allow the come back of proteins and RNAs into the organelle. Paradoxically, the few mitochondria-encoded protein genes remain essential and must be translated by a mitochondrial translation machinery mainly constituted by nucleus-encoded components. Two crucial partners of the mitochondrial translation machinery are the aminoacyl-tRNA synthetases and the tRNAs. All mitochondrial aminoacyl-tRNA synthetases and many tRNAs are imported from the cytosol into the mitochondria in eukaryotic cells. During the last few years, their origin and their import into the organelle have been studied in evolutionary distinct organisms and we review here what is known in this field.
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TL;DR: The current knowledge of routes to functional diversity and DNA binding specificity is presented, including divergent properties of the conserved ETS and PNT domains, the involvement of flanking structured and unstructured regions appended to these dynamic domains, posttranslational modifications, and protein partnerships with other DNA-binding proteins and coregulators.
Abstract: ETS proteins are a group of evolutionarily related, DNA-binding transcriptional factors. These proteins direct gene expression in diverse normal and disease states by binding to specific promoters and enhancers and facilitating assembly of other components of the transcriptional machinery. The highly conserved DNA-binding ETS domain defines the family and is responsible for specific recognition of a common sequence motif, 5 � -GGA(A/T)-3 � . Attaining specificity for biological regulation in such a family is thus a conundrum. We present the current knowledge of routes to functional diversity and DNA binding specificity, including divergent properties of the conserved ETS and PNT domains, the involvement of flanking structured and unstructured regions appended to these dynamic domains, posttranslational modifications, and protein partnerships with other DNA-binding proteins and coregulators. The review emphasizes recent advances from biochemical and biophysical approaches, as well as insights from genomic studies that detect ETSfactor occupancy in living cells.
434 citations
Cites background from "Import of tRNAs and aminoacyl-tRNA ..."
...thaliana that are dually targeted to the mitochondria and the cytosol aminoacylate imported tRNAs (98, 99)....
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TL;DR: It is reported that miR-1, a microRNA specifically induced during myogenesis, efficiently enters the mitochondria where it unexpectedly stimulates, rather than represses, the translation of specific mitochondrial genome-encoded transcripts.
373 citations
TL;DR: PNPASE RNA processing and import activities were separable and a mitochondrial RNA targeting signal was isolated that enabled RNA import in a PNPASE-dependent manner, and these data strongly support an unanticipated role for P NPASE in mediating the translocation of RNAs into mitochondria.
302 citations
Cites background from "Import of tRNAs and aminoacyl-tRNA ..."
...Critical open questions about RNA import into mammalian mitochondria include the selectivity of RNAs, the factor(s) targeting RNA from the cytosol, and the translocation pathway(s) across the mitochondrial membranes (Duchene et al., 2009)....
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...Almost every organism with mitochondria imports tRNAs and aminoacyl-tRNA synthetases (Alfonzo and Soll, 2009; Duchene et al., 2009)....
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TL;DR: The present study experimentally demonstrated the presence of pre-miRNA and miRNA in the human mitochondria isolated from skeletal muscular cells and a set of miRNA were significantly detected in mitochondria fraction.
Abstract: Background Because of the central functions of the mitochondria in providing metabolic energy and initiating apoptosis on one hand and the role that microRNA (miRNA) play in gene expression, we hypothesized that some miRNA could be present in the mitochondria for post-transcriptomic regulation by RNA interference. We intend to identify miRNA localized in the mitochondria isolated from human skeletal primary muscular cells. Methodology/Principal Findings To investigate the potential origin of mitochondrial miRNA, we in-silico searched for microRNA candidates in the mtDNA. Twenty five human pre-miRNA and 33 miRNA aligments (E-value 35) for the smallest RNA input concentration and 204 miRNA for the maximum RNA input concentration. In silico analysis predicted 80 putative miRNA target sites in the mitochondrial genome (E-value<0.05). Conclusions/Significance The present study experimentally demonstrated for the first time the presence of pre-miRNA and miRNA in the human mitochondria isolated from skeletal muscular cells. A set of miRNA were significantly detected in mitochondria fraction. The origin of these pre-miRNA and miRNA should be further investigate to determine if they are imported from the cytosol and/or if they are partially processed in the mitochondria.
267 citations
Cites background from "Import of tRNAs and aminoacyl-tRNA ..."
...The importation of tRNA in the mitochondria is a natural process that could also play a role for the mitochondrial miRNA importation [29,30]....
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TL;DR: This work has shown that hybridization brings together previously untested allelic combinations and can disrupt intergenomic coadaptation, resulting in organelle dysfunction and, consequen...
Abstract: Reduced fitness in interpopulation hybrids can be a first indication of genetic incompatibilities that may ultimately lead to reproductive isolation and speciation. A growing number of cases of hybrid breakdown have been traced to incompatibilities between the nuclear genome and the organellar genomes of the mitochondria and chloroplasts. Although these organellar genomes derive from ancient bacterial endosymbioses, they have been vastly reduced in size and now encode relatively few genes. The remaining genes are necessary but not sufficient for organelle function. In fact, most proteins functioning in the organelles are encoded in the nuclear genome and need to be imported after synthesis in the cytosol. The necessary interactions between organelle and nuclear genomes have resulted in some degree of coadaptation within all natural populations. Hybridization brings together previously untested allelic combinations and can disrupt intergenomic coadaptation, resulting in organelle dysfunction and, consequen...
240 citations
References
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TL;DR: A reference database or "compendium" of expression profiles corresponding to 300 diverse mutations and chemical treatments in S. cerevisiae is constructed, and it is shown that the cellular pathways affected can be determined by pattern matching, even among very subtle profiles.
2,698 citations
"Import of tRNAs and aminoacyl-tRNA ..." refers background in this paper
...Interestingly, orthologs of the GatA and GatB subunits of a potential tRNA-dependent amidotransamidase have been identiWed in yeast (YMR293C and PET112 respectively) (Mulero et al. 1994; Hughes et al. 2000)....
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University of California, Los Angeles1, United States Department of Energy2, University of Paris3, Duke University4, University of Massachusetts Medical School5, University of California, Berkeley6, Centre national de la recherche scientifique7, University of California, San Francisco8, Sun Yat-sen University9, University of Tennessee Health Science Center10, University of Minnesota11, Iowa State University12, Genetic Information Research Institute13, Salk Institute for Biological Studies14, Stanford University15, University of Liège16, University of Nebraska–Lincoln17, University of Cambridge18, Washington University in St. Louis19, University of Córdoba (Spain)20, Kyoto University21, Carnegie Institution for Science22, National Autonomous University of Mexico23, University of Münster24, École Normale Supérieure25, University of Melbourne26, University of Paris-Sud27, University of Mainz28, Scripps Research Institute29, Ohio State University30, University of Chicago31, University of Jena32, University of Arizona33, Louisiana State University34, University of New Brunswick35, University College London36, University of Potsdam37, Delaware Biotechnology Institute38, Boyce Thompson Institute for Plant Research39, Macquarie University40, Oklahoma State University Center for Health Sciences41, İzmir University of Economics42, Academy of Sciences of the Czech Republic43, Charles University in Prague44, St. Edward's University45, University of Puget Sound46, Hokkaido University47, Tsinghua University48, Washington State University49, Appalachian State University50, Marquette University51
TL;DR: Analyses of the Chlamydomonas genome advance the understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.
Abstract: Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the approximately 120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.
2,554 citations
Wellcome Trust Sanger Institute1, George Washington University2, J. Craig Venter Institute3, University of Glasgow4, University of Oxford5, Newcastle University6, University of Bordeaux7, University of Cambridge8, Oregon Health & Science University9, University of Dundee10, Imperial College London11, Case Western Reserve University12, Yale University13, Université catholique de Louvain14, University of Iowa15, Wellcome Trust16
TL;DR: Comparisons of the cytoskeleton and endocytic trafficking systems of Trypanosoma brucei with those of humans and other eukaryotic organisms reveal major differences.
Abstract: African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including ∼900 pseudogenes and ∼1700 T. brucei–specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.
1,631 citations
"Import of tRNAs and aminoacyl-tRNA ..." refers background in this paper
...Trypanosomatid mitochondrial aaRSs Twenty-six and 23 aaRS sequences are annotated in Trypanosoma brucei and Leishmania major genomes respectively (www.sanger.ac.uk/; www.genedb.org/) (Berriman et al. 2005; Ivens et al. 2005)....
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TL;DR: This review explores the advances that have been made and the areas in which future progress is likely in understanding basic mitochondrial genetics and the relationship between inherited mutations and disease phenotypes, and in identifying acquired mtDNA mutations in both ageing and cancer.
Abstract: The human mitochondrial genome is extremely small compared with the nuclear genome, and mitochondrial genetics presents unique clinical and experimental challenges. Despite the diminutive size of the mitochondrial genome, mitochondrial DNA (mtDNA) mutations are an important cause of inherited disease. Recent years have witnessed considerable progress in understanding basic mitochondrial genetics and the relationship between inherited mutations and disease phenotypes, and in identifying acquired mtDNA mutations in both ageing and cancer. However, many challenges remain, including the prevention and treatment of these diseases. This review explores the advances that have been made and the areas in which future progress is likely.
1,525 citations
Wellcome Trust Sanger Institute1, Seattle Biomed2, Katholieke Universiteit Leuven3, GATC Biotech4, Max Planck Society5, Washington University in St. Louis6, University of Trieste7, International Centre for Genetic Engineering and Biotechnology8, European Bioinformatics Institute9, University of São Paulo10, National Scientific and Technical Research Council11, Université catholique de Louvain12, University of London13, University of Edinburgh14, University of Glasgow15, University of Wisconsin-Madison16, University of York17, University of Cambridge18, University of Washington19
TL;DR: The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Tritryp genomes suggest that the mechanisms regulating RNA polymerase II–directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling.
Abstract: Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.
1,357 citations