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At least 19 recordsLinked to original sources
PubMed1995

RNase mitochondrial RNA processing cleaves RNA from the rat mitochondrial displacement loop at the origin of heavy-strand DNA replication.

Ribonuclease mitochondrial RNA processing cleaves RNAs from the mammalian mitochondrial main non-coding regulatory region, called the displacement loop. Our data demonstrate that rat cells contain a site-specific ribonuclease mitochondrial RNA processing activity. We found that this enzyme processes the rat mitochondrial displacement-loop RNA substrate at the level of the conserved sequence block 1, a result which is different from that for mouse. This finding correlates with the in-vivo transcriptional analysis of the rat displacement-loop region. Processing by homologous and heterologous ribonuclease mitochondrial RNA enzymes occurs in the same manner, suggesting a conserved mode of substrate recognition.

Animals↗
PubMed1987

A mammalian mitochondrial RNA processing activity contains nucleus-encoded RNA.

Ribonuclease mitochondrial RNA processing, a site-specific endoribonuclease involved in primer RNA metabolism in mammalian mitochondria, requires an RNA component for its activity. On the basis of copurification and selective inactivation with complementary oligonucleotides, a 135-nucleotide RNA species, not encoded in the mitochondrial genome, is identified as the RNA moiety of the endoribonuclease. This finding implies transport of a nucleus-encoded RNA, essential for organelle DNA replication, to the mitochondrial matrix.

Animals↗
PubMed1997

Reduced steady-state levels of mitochondrial RNA and increased mitochondrial DNA amount in human brain with aging.

The contribution of the mitochondrial genetic system in the degenerative processes of senescence remains unclear. This study deals with age-related changes in brain mtDNA expression in humans. Brain tissue from the frontal lobe cortex was obtained from autopsy of 13 humans aged between 21 and 84 years. No structural changes were detected in mtDNA, increased mtDNA content and reduced steady-state level of mitochondrial transcripts and transcription ratio (mtRNA/mtDNA) were associated with aging. These findings suggest that the increase of the mtDNA levels could be considered as an inefficient compensatory mechanism to maintain the normal levels of mtRNA transcripts. This unbalanced mitochondrial condition could play a role in the process of senescence in human brain.

Adult↗
PubMed1999

Stability of the mitochondrial genome requires an amino-terminal domain of yeast mitochondrial RNA polymerase.

Mitochondrial RNA (mtRNA) polymerases are related to bacteriophage RNA polymerases, but contain a unique amino-terminal extension of unknown origin and function. In addition to harboring mitochondrial targeting information, we show here that the amino-terminal extension of yeast mtRNA polymerase is required for a mtDNA maintenance function that is separable from the known RNA polymerization activity of the enzyme. Deletion of 185 N-terminal amino acids from the enzyme results in a temperature-sensitive mitochondrial petite phenotype, characterized by increased instability and eventual loss of the mitochondrial genome. Mitochondrial transcription initiation in vivo is largely unaffected by this mutation and expression of just the amino-terminal portion of the protein in trans partially suppresses the mitochondrial defect, indicating that the amino-terminal extension of the enzyme harbors an independent functional domain that is required for mtDNA replication and/or stability. These results suggest that amino-terminal extensions present in mtRNA polymerases comprise functional domains that couple additional activities to the transcription process in mitochondria.

Bacteriophages↗
PubMed2001

Identification and characterization of a Plasmodium falciparum RNA polymerase gene with similarity to mitochondrial RNA polymerases.

Nearly all mitochondrial RNA polymerase genes identified to date are encoded in the nucleus and have similarities to T3 and T7 bacteriophage RNA polymerases. Some chloroplast genes are also transcribed by T3/T7 phage-like RNA polymerases, raising the possibility that the apicomplexan parasites, which have both a mitochondrion and a plastid, might have two such genes. As part of an investigation of Plasmodium falciparum organelle transcription, we initiated a search for T3/T7 bacteriophage-like RNA polymerase genes. We employed degenerate primers based on highly conserved plant, animal and fungal mitochondrial RNA polymerase sequences to amplify corresponding P. falciparum sequences by polymerase chain reaction (PCR). Less well-conserved flanking sequences were obtained by inverse PCR. The resulting sequence predicts a 1503 amino acid open reading frame with similarity to other T3/T7 phage-like RNA polymerases. Essential amino acids that have been identified in T7 mutant analyses are conserved in the P. falciparum RNA polymerase gene. Comparison of the sequence with preliminary data from the P. falciparum genome sequencing project revealed strain heterogeneity within two regions of the gene. The amino-terminal predicted amino acid sequence of the RNA polymerase gene has similarities to mitochondrial targeting sequences. Taken together, these points suggest that we have identified the P. falciparum mitochondrial RNA polymerase gene.

Amino Acid Sequence↗
PubMed2004

TbDSS-1, an essential Trypanosoma brucei exoribonuclease homolog that has pleiotropic effects on mitochondrial RNA metabolism.

Mitochondrial gene expression in trypanosomes is controlled primarily at the levels of RNA processing and RNA stability. This regulation undoubtedly involves numerous ribonucleases. Here we characterize the Trypanosoma brucei homolog of the yeast DSS-1 mitochondrial exoribonuclease, which we term TbDSS-1. Biochemical fractionation indicates that TbDSS-1 is mitochondrially localized, as predicted by its N-terminal sequence. In contrast to its yeast homolog, TbDSS-1 does not appear to be associated with mitochondrial ribosomes. Targeted downregulation of TbDSS-1 by RNA interference in procyclic-form T. brucei results in a severe growth defect. In addition, TbDSS-1 depletion leads to a decrease in the levels of never edited cytochrome oxidase subunit I (COI) mRNA and both unedited and edited COIII mRNAs, indicating this enzyme functions in the control of mitochondrial RNA abundance. We also observe a considerable reduction in the level of edited apocytochrome b (CYb) mRNA and a corresponding increase in unedited CYb mRNA, suggesting that TbDSS-1 functions, either directly or indirectly, in the control of RNA editing. The abundance of both gCYb[560] and gA6[149] guide RNAs is reduced upon TbDSS-1 depletion, although the reduction in gCYb[560] is much more dramatic. The significant reduction in gCYb levels could potentially account for the observed decrease in CYb RNA editing. Western blot analyses of mitochondrial RNA editing and stability factors indicate that the perturbations of RNA levels observed in TbDSS-1 knock-downs do not result from secondary effects on other mitochondrial proteins. In all, these data demonstrate that TbDSS-1 is an essential protein that plays a role in mitochondrial RNA stability and RNA editing.

Amino Acid Sequence↗
PubMed2006

Mutations in the RNA component of RNase mitochondrial RNA processing might cause Omenn syndrome.

BACKGROUND: Omenn syndrome is a variant of severe combined immunodeficiency disease, which most prominently presents with erythroderma, eosinophilia, and susceptibility to various pathogens. Mutations in the nucleases of recombination activating genes 1 and 2 (RAG1/RAG2) or Artemis were found in some, but not all, patients with Omenn syndrome. We identified 2 patients who presented with clinical features consistent with Omenn syndrome but had no mutations in RAG or Artemis. Both patients also had cartilage-hair hypoplasia (CHH). OBJECTIVES: We sought to define the molecular basis and characterize the features of severe combined immunodeficiency and Omenn syndrome in these patients. METHODS: We have studied humoral and cellular immunity using standard assays. T-cell repertoire was investigated by quantitating Vbeta families. The RNase mitochondrial RNA processing (RMRP) RNA gene was sequenced by using standard techniques. RESULTS: Sequence analysis of the RMRP RNA gene showed that each patient had an insertion-duplication on one allele and a point mutation on the other allele. These point mutations were novel, and they might be related to the unusual presentation of Omenn syndrome in addition to CHH in these patients. Indeed, analysis of the thymus showed residual mature T lymphocytes. This leaky thymus might be responsible for the skewed release of some T-cell clones into the circulation, which might trigger the phenotype of Omenn syndrome. CONCLUSION: We have demonstrated that mutations in the RMRP RNA gene might be associated with Omenn syndrome. CLINICAL IMPLICATIONS: This discovery will aid clinicians in the early recognition and treatment of CHH-associated Omenn syndrome.

Base Sequence↗
PubMed1998

Decreased mitochondrial RNA levels without accumulation of mitochondrial DNA deletions in aging Drosophila melanogaster.

Declines in electron transport system (ETS) activity have been reported to occur with advancing age in Drosophila melanogaster and many other animals. It has been proposed that these changes are importantly involved in the aging process. ETS decline has been attributed to mitochondrial nucleic acid damage. We analyzed various ages of D. melanogaster (embryos to 60-day-old adults) for the presence of mutated mitochondrial DNA (mtDNA) genomes. Although mtDNA genomes with large DNA deletions (up to 5 kb) were identified, abundance was low and remained constant throughout adult life. Therefore, these mtDNA deletions do not appear to be sufficiently abundant to cause large declines in ETS activity. Next, we analyzed various ages of D. melanogaster for the abundance of four mitochondrial-encoded and two nuclear-encoded ETS transcripts. The abundance of the mitochondrial transcripts declined 5-10-fold, while the nuclear-encoded transcripts declined 2-5-fold with advancing age. Separation of flies on the basis of flight loss was used to distinguish physiologic age from chronological age. Insects capable of flight at 30 days of age were found to have a 4-fold higher abundance of cox I mitochondrial-encoded RNA compared to flightless insects. No difference, however, was apparent in the nuclear-encoded beta-ATPase RNA level, suggesting only mitochondrial RNA (mtRNA) declines are associated with life expectancy.

Aging↗
PubMed1989

Mutations in the genes for mitochondrial RNA polymerase and a second mitochondrial transcription factor of Saccharomyces cerevisiae.

In our previous work (Lisowsky et al. 1987; Lisowsky and Michaelis 1988) we have identified two nuclear pet genes of yeast that are required for mitochondrial transcription. In this report we show that one of these pet mutations, pet-ts798, maps in the RP041 gene encoding mitochondrial RNA polymerase. The temperature-sensitive lesion of mutant pet-ts798 can be suppressed by a second nuclear gene RF1023 (mtf1) when inserted into a high copy number plasmid. Our assumption that mtf1 codes for a 40 kDa mitochondrial transciription factor is supported by the fact that the cloned gene acts as an intergenic suppressor of a temperature-sensitive RNA polymerase mutant. A third nuclear gene (mtf2) for mitochondrial transcription was identified by analysing mutant pet-ts3504. The in vitro transcriptional activity of isolated mutant mitochondria is temperature sensitive suggesting the presence of an altered component of transcription inside mitochondria. The defect was confirmed by studies with a transcriptionally active DNA-protein complex and by testing the DNA-binding ability of mitochondrial proteins.

Alleles↗
PubMedDate not supplied

[The time-dependent stimulating action of hydrocortisone on mitochondrial RNA biosynthesis in the rat liver].

Mitochondrial RNA biosynthesis was studied at different time after hydrocortisone administration. Hydrocortisone induced liver mitochondrial RNA biosynthesis in vivo and in isolated organellae 15 min., 1.5 and 4 h after hormone injection. As shown by means of molecular hybridization of RNA-DNA, an increase in liver mitochondrial RNA biosynthesis induced by hydrocortisone administration was due to an increase in the expression of all mitochondrial genes simultaneously rather than to selective enhancement of individual gene transcription. Hydrocortisone changed the biosynthesis and transport of cytoplasmic RNA in the liver of intact rats. The incorporation of 3H-UTP into RNA by isolated liver mitochondria of control and hydrocortisone-treated rats was inhibited by ethidium bromide. RNA biosynthesis in isolated rat liver mitochondria was unchanged in 15-300 min. of 0.9% NaCl administration.

Animals↗
PubMed1997

Unusual usage of noncomplementary dinucleotide primers by the yeast mitochondrial RNA polymerase.

The mitochondrial RNase P RNA gene in yeast Saccharomyces cerevisiae is transcribed from a variant mitochondrial promoter (SP). The sequence of this SP promoter [TATAAGAAG (+2)] differs from the conserved mitochondrial promoter sequence [TATAAGTAA (+2)] by-1T-->A and +2A-->G nucleotide substitutions. To determine the effect of these nucleotide alterations in mitochondrial promoter function, an in vitro transcription analysis was carried out. In the presence of high concentrations of rNTPs (i.e., 125 microM), transcription initiation on the wild-type or variant promoter occurred at the conventional 3' adenine nucleotide. However, at low rNTP concentrations (i.e., 5 microM) and in the presence of a complementary dinucleotide primer corresponding to positions -1 + 1, the mitochondrial RNA polymerase started transcription one nucleotide upstream of the conventional start site. Surprisingly, in the presence of some noncomplementary dinucleotides (i.e., GpA or CpA), which do not have perfect Watson-Crick base pairing with the initiator sequence, transcriptional initiation also occurred with the SP promoter but not with the conserved promoter sequence. This finding is the first example of utilization of noncomplementary dinucleotide primer by an RNA polymerase. Further analysis of mitochondrial promoter function by site-directed mutagenesis determined that the guanine nucleotide at position +2 is mainly responsible for this unusual function of the SP promoter.

DNA-Directed RNA Polymerases↗
PubMed1993

Alterations in mitochondrial RNA expression after renal ischemia.

Ischemia and reperfusion damage mitochondrial structure and impair respiratory function. In this study, 45 min of renal ischemia followed by varying periods of reflow profoundly depressed the activity of several respiratory complexes in mitochondria isolated from rat kidneys. The respiratory complexes are composed of subunits encoded by both the nuclear and mitochondrial genomes. To determine the role of mitochondrial gene expression in recovery of respiratory function, expression of mitochondrial RNA was examined during reperfusion. Both mature and incompletely processed cytochrome b mRNA levels were depressed after 45 min of ischemia and 15 min of reflow; levels rebounded to above normal after 2 h of reflow and then declined over the next 22 h. Another mitochondrial RNA showed a similar pattern; in contrast, the levels of a nuclear-encoded subunit mRNA for a respiratory enzyme and of 28S rRNA were unchanged. These data demonstrate that renal ischemia followed by reperfusion alters mitochondrial RNA expression. We speculate that mitochondrial RNA turnover is increased in response to continuing injury and that recovery is accompanied by enhanced RNA synthesis.

Animals↗
PubMed1983

Determination of functional domains in intron bI1 of yeast mitochondrial RNA by studies of mitochondrial mutations and a nuclear suppressor.

The sequence of intron 1 in the cob gene in mtDNA (bI1) of the yeast strain 777-3A has been determined. Furthermore, we have performed a systematic search for complementary sequence stretches within this intron RNA, and within the RNA of intron 5 gamma of the oxi3 gene (aI5 gamma) which shares distinctive sequences with bI1. Possible secondary structure models derived from this analysis show nearly identical core structures for bI1 and aI5 gamma RNA with conserved sequence stretches in prominent positions. These core structures are similar to those previously reported for RNAs of introns having very limited sequence homology with bI1 and aI5 gamma. In two mutants which are defective in bI1 excision from cob pre-mRNA, nucleotide sequence alterations in bI1 have been determined. One mutation (G5049) apparently affects the stability of a hybrid stretch in the proposed secondary structure of bI1 RNA whereas the other one (M1301), a deletion of one A in a run of five As, affects a sequence which is conserved in bI1 and aI5 gamma and is involved in the formation of a distinct secondary structure. Out of seven revertants of M1301, three were found to have restored the wild-type bI1 sequence AAAAA, three others had the related sequence AAAAG which is functionally indistinguishable from wild-type, whereas one revertant had a nuclear mutation which suppresses the splicing defect exerted by the mitochondrial mutation M1301. This nuclear suppressor (SUP-101) is allele specific and dominant. The possible role of the sequence affected by M1301 in terms of a recognition site for a nuclear gene product will be discussed.

Base Sequence↗
PubMed1987

Synthesis and turnover rates of four rat liver mitochondrial RNA species.

The synthesis and turnover rates of the two 12 S and 16 S mt rRNAs and of the mt mRNAs for subunits I and III of cytochrome oxidase have been determined by measuring the kinetics of incorporation of [3H]uridine in the mtRNA of rat hepatocytes. All the RNA species examined have approximately the same turnover (t1/2 approximately 100 min) and therefore the rate of synthesis, which is about 10-times higher for the rRNAs, seems to be the factor responsible for the different mt rRNA and mRNA steady-state levels.

Animals↗