Transcription mapping of the Ori L region reveals novel precursors of mature RNA species and antisense RNAs in rat mitochondrial genome

Sbisà, Elisabetta; Tullo, Apollonia; Nardelli, Maria; Tanzariello, F.; Saccone, Cecilia

doi:10.1016/0014-5793(92)80311-4

Cited by 31 publications

(21 citation statements)

References 16 publications

(1 reference statement)

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“…It is noteworthy that the 3.6-kb ND5 ϩ Cyt-b precursor was the mitochondrial mRNA most affected by hypoxia. Stable polyadenylated mitochondrial mRNA molecules that are precursors of the mature species have been found before (57,58). Our results thus strengthen the concept that stepwise processing of the polycistronic transcripts is an additional regulatory element in the expression of the mitochondrial genome.…”

Section: Discussionsupporting

confidence: 83%

Oxygen Tension Regulates Mitochondrial DNA-encoded Complex I Gene Expression

Piruat

López‐Barneo

2005

Journal of Biological Chemistry

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Oxygen is a major regulator of nuclear gene expression. However, although mitochondria consume almost all of the O 2 available to the cells, little is known about how O 2 tension influences the expression of the mitochondrial genome. We show in O 2 -sensitive excitable rat PC12 cells that, among the mtDNA-encoded genes, hypoxia produced a specific down-regulation of the transcripts encoding mitochondrial complex I NADH dehydrogenase (ND) subunits, particularly ND4 and ND5 mRNAs and a stable mRNA precursor containing the ND5 and cytochrome b genes. This unprecedented effect of hypoxia was fast (developed in <30 min) and fairly reversible and occurred at moderate levels of hypoxia (O 2 tensions in the range of 20 -70 mm Hg). Hypoxic down-regulation of the mitochondrial complex I genes was paralleled by the reduction of complex I activity and was retarded by iron chelation, suggesting that an iron-dependent post-transcriptional mechanism could regulate mitochondrial mRNA stability. It is known that cell respiration is under tight control by the amount of proteins in mitochondrial complexes of the electron transport chain. Therefore, regulation of the expression of the mitochondrial (mtDNA)-encoded complex I subunits could be part of an adaptive mechanism to adjust respiration rate to the availability of O 2 and to induce fast adaptive changes in hypoxic cells.Oxygen (O 2 ) is absolutely required for cell survival due to its fundamental role in mitochondrial oxidative phosphorylation. Decreases in O 2 tension (PO 2 ) trigger acute and chronic adaptive cellular responses to increase O 2 delivery to the tissues and to minimize the deleterious effects of hypoxia. In mammals, acute hypoxia (occurring over a time scale of seconds to minutes) regulates the activity of ion channels existing in specific O 2 -sensitive cells, which mediate fast respiratory and cardiovascular counterregulatory adjustments (for review, see Refs. 1 and 2 and references therein). Protracted (chronic) hypoxia (lasting hours or days) activates hypoxia-inducible transcription factors (hypoxia-inducible factor-1␣ (HIF-1␣) 2 and isoforms) that regulate the expression of a broad and growing set of nuclear genes involved in anaerobic glucose metabolism, angiogenesis, or oxygen transport as well as in development, tissue remodeling, and tumor transformation (3-5).In recent years, it has been shown that HIF activity depends on prolyl and asparaginyl hydroxylases, which utilize ambient O 2 as substrate. Under normoxic conditions, hydroxylation of proline and asparagine accelerates HIF-1␣ degradation by the proteasome (6, 7) and prevents its transcriptional activity (8, 9). Inhibition of HIF-1␣ hydroxylation during hypoxia leads to its stabilization and nuclear translocation and to the subsequent activation of HIF-dependent genes (10 -12). Stabilization of HIF-1␣ by hypoxia seems to require the release of reactive oxygen species (ROS) from mitochondria to the cytosol (13-16).Despite the progress in the understanding of the signaling pathway responsible for...

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Section: Discussionsupporting

confidence: 83%

Oxygen Tension Regulates Mitochondrial DNA-encoded Complex I Gene Expression

Piruat

López‐Barneo

2005

Journal of Biological Chemistry

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“…In this process, the order of the cleavage events may play a determining role. In vitro tRNA processing experiments (36) and in vivo observations (12,37) have indicated that the order of 5Ј-and 3Ј-end cleavages of the tRNA precursors in human mitochondria may vary depending on the tRNA. Other in vitro processing experiments utilizing partially purified mitochondrial RNase P from HeLa cells have shown that a tRNA Ser(UCN) precursor carrying a 3Ј-terminal CCA is accurately cleaved by the enzyme at the 5Ј end of the tRNA (32a).…”

Section: Discussionmentioning

confidence: 99%

The Deafness-Associated Mitochondrial DNA Mutation at Position 7445, Which Affects tRNA^Ser(UCN) Precursor Processing, Has Long-Range Effects on NADH Dehydrogenase Subunit ND6 Gene Expression

Guan

Enrı́quez

Fischel‐Ghodsian

et al. 1998

Molecular and Cellular Biology

184

185

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The pathogenetic mechanism of the deafness-associated mitochondrial DNA (mtDNA) T7445C mutation has been investigated in several lymphoblastoid cell lines from members of a New Zealand pedigree exhibiting the mutation in homoplasmic form and from control individuals. We show here that the mutation flanks the 3 end of the tRNA Ser(UCN) gene sequence and affects the rate but not the sites of processing of the tRNA precursor. This causes an average reduction of ϳ70% in the tRNA Ser(UCN) level and a decrease of ϳ45% in protein synthesis rate in the cell lines analyzed. The data show a sharp threshold in the capacity of tRNA Ser(UCN) to support the wild-type protein synthesis rate, which corresponds to ϳ40% of the control level of this tRNA. Strikingly, a 7445 mutation-associated marked reduction has been observed in the level of the mRNA for the NADH dehydrogenase (complex I) ND6 subunit gene, which is located ϳ7 kbp upstream and is cotranscribed with the tRNA Ser(UCN) gene, with strong evidence pointing to a mechanistic link with the tRNA precursor processing defect. Such reduction significantly affects the rate of synthesis of the ND6 subunit and plays a determinant role in the deafness-associated respiratory phenotype of the mutant cell lines. In particular, it accounts for their specific, very significant decrease in glutamate-or malate-dependent O 2 consumption. Furthermore, several homoplasmic mtDNA mutations affecting subunits of NADH dehydrogenase may play a synergistic role in the establishment of the respiratory phenotype of the mutant cells.

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“…However, the lack of nontranscribed regulatory regions is not surprising in mtDNA. In mammals, both the noncoding regulatory regions, that is, the large D-loop containing region and the small L-strand replication origin, have been detected among the transcribed sequences as sense and antisense RNAs, and such transcripts are probably implicated in the regulation of mtDNA replication and expression (Sbisa et al 1990(Sbisa et al , 1992.…”

Section: Transcript Mapping Of Ascidian Mtdna With Est Datamentioning

confidence: 99%

Transcript Mapping and Genome Annotation of Ascidian mtDNA Using EST Data

Gissi

Pesole²

2003

Genome Res.

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Mitochondrial transcripts of two ascidian species were reconstructed through sequence assembly of publicly available ESTs resembling mitochondrial DNA sequences (mt-ESTs). This strategy allowed us to analyze processing and mapping of the mitochondrial transcripts and to investigate the gene organization of a previously uncharacterized mitochondrial genome (mtDNA). This new strategy would greatly facilitate the sequencing and annotation of mtDNAs. In Ciona intestinalis, the assembled mt-ESTs covered 22 mitochondrial genes (∼12,000 bp) and provided the partial sequence of the mtDNA and the prediction of its gene organization. Such sequences were confirmed by amplification and sequencing of the entire Ciona mtDNA. For Halocynthia roretzi, for which the mtDNA sequence was already available, the inferred mt transcripts allowed better definition of gene boundaries (16S rRNA, ND1, ATP6, and tRNA-Ser genes) and the identification of a new gene (an additional Phe-tRNA). In both species, polycistronic and immature transcripts, creation of stop codons by polyadenylation, tRNA signal processing, and rRNA transcript termination signals were identified, thus suggesting that the main features of mitochondrial transcripts are conserved in Chordata.

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Transcription mapping of the Ori L region reveals novel precursors of mature RNA species and antisense RNAs in rat mitochondrial genome

Cited by 31 publications

References 16 publications

Oxygen Tension Regulates Mitochondrial DNA-encoded Complex I Gene Expression

Oxygen Tension Regulates Mitochondrial DNA-encoded Complex I Gene Expression

The Deafness-Associated Mitochondrial DNA Mutation at Position 7445, Which Affects tRNA^Ser(UCN) Precursor Processing, Has Long-Range Effects on NADH Dehydrogenase Subunit ND6 Gene Expression

Transcript Mapping and Genome Annotation of Ascidian mtDNA Using EST Data

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Transcription mapping of the Ori L region reveals novel precursors of mature RNA species and antisense RNAs in rat mitochondrial genome

Cited by 31 publications

References 16 publications

Oxygen Tension Regulates Mitochondrial DNA-encoded Complex I Gene Expression

Oxygen Tension Regulates Mitochondrial DNA-encoded Complex I Gene Expression

The Deafness-Associated Mitochondrial DNA Mutation at Position 7445, Which Affects tRNASer(UCN) Precursor Processing, Has Long-Range Effects on NADH Dehydrogenase Subunit ND6 Gene Expression

Transcript Mapping and Genome Annotation of Ascidian mtDNA Using EST Data

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The Deafness-Associated Mitochondrial DNA Mutation at Position 7445, Which Affects tRNA^Ser(UCN) Precursor Processing, Has Long-Range Effects on NADH Dehydrogenase Subunit ND6 Gene Expression