Detection of novel transcripts in the human mitochondrial DNA region coding for ATPase8—ATPase6 subunits

Nardelli, Maria; Tommasi, Stefania; D’Erchia, Anna Maria; Tanzariello, F.; Tullo, Apollonia; Primavera, Anna Teresa; Lena, M. De; Sbisà, Elisabetta; Saccone, Cecilia

doi:10.1016/0014-5793(94)00342-4

Cited by 14 publications

(10 citation statements)

References 15 publications

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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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“…4c). As in the case of precursor RNAs reported by us in human [6], termination codons present upstream the initiation codon prevent the translation of a product longer than the mature mRNA. The finding of this precursor confirms our previous hypothesis that the processing proceeds stepwise [5,6].…”

Section: Discussionmentioning

confidence: 98%

“…As in the case of precursor RNAs reported by us in human [6], termination codons present upstream the initiation codon prevent the translation of a product longer than the mature mRNA. The finding of this precursor confirms our previous hypothesis that the processing proceeds stepwise [5,6]. Precursor products are likely to have functional consequences on the expression of the mammalian mitochondrial genome and to play a role in development and disease [27].…”

Section: Discussionmentioning

confidence: 98%

“…In the ourse of our recent studies on the mammalian mitochondrial enome and its expression, we have discovered new aspects and :atures of mt transcription. We have identified RNAs, which re precursors of the mature species, in the Ori L region in rat nd in the ATPase region in human, demonstrating that the lrocessing of the polycistronic transcripts occurs by steps [5,6]. 'hese data have led us to consider the processing mechanism s a further possible regulatory element in the expression of the nt genome.…”

Section: Introductionmentioning

confidence: 99%

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Transcription of rat mitochondrial NADH‐dehydrogenase subunits presence of antisense and precursor RNA species

et al. 1994

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bstract We have characterized the transcriptional pattern of the rat mitochondrial ND6containing region in vivo. We have identified a stable nyadenylated RNA species complementary for the full length of the ND6 mRNA. The analysis of the ND5 region has revealed the presence of I antisense RNA only at its 3' end. The presence of these stable antisense species complementary to structural genes is intriguing and suggests a rssible regulatory function. The quantitative analyses have demonstrated that the H transcripts, both codogenic and non-codogenic, are more stable an the L transcriptswe have defined the 5' end of the ND6 mRNA at the level of the ATG downstream of the tRNAo'". The mapping of the ND1 end has demonstrated that GTG is the first codon of the mRNA. Our findings suggest that the post-transcriptional mechanisms involved in the pression of the mt genome are much more numerous and complex than those already described in the literature.

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“…The non‐ redundant mitochondrial transcripts covered about 30% (4964 bp) of the porcine mitochondrial genome. Of particular interest is the presence of mitochondrial ATPase8/ATPase6 hybrid cDNAs that were previously identified in human (Nardelli et al . 1994).…”

Section: Discussionmentioning

confidence: 99%

Isolation of porcine expressed sequence tags for the construction of a first genomic transcript map of the skeletal muscle in pig

et al. 2002

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To identify genes with effects on meat quality and production traits we developed an adult porcine skeletal muscle cDNA library. After pre-screening this library with seven genes highly expressed in skeletal muscle, 385 non-hybridizing clones were sequenced from both ends to yield 510 expressed sequence tags (ESTs). Together with those ESTs previously generated from this library, we have produced 701 porcine skeletal muscle ESTs. These ESTs were grouped into 306 different cDNA species and compared with the human skeletal muscle transcriptional profiles obtained from different databases. Furthermore we mapped 107 of these cDNAs using a somatic cell hybrid panel with genes mapping over all the autosomes (except on chromosome 11) and on chromosome X. The mapping of these cDNAs contributed to the construction of a first genomic transcript map of the skeletal muscle tissue in pig.

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Detection of novel transcripts in the human mitochondrial DNA region coding for ATPase8—ATPase6 subunits

Cited by 14 publications

References 15 publications

Oxygen Tension Regulates Mitochondrial DNA-encoded Complex I Gene Expression

Oxygen Tension Regulates Mitochondrial DNA-encoded Complex I Gene Expression

Transcription of rat mitochondrial NADH‐dehydrogenase subunits presence of antisense and precursor RNA species

Isolation of porcine expressed sequence tags for the construction of a first genomic transcript map of the skeletal muscle in pig

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