title: Cloning of the human mitochondrial 51 kDa subunit (NDUFV1) reveals a 100% antisense homology of its 3'UTR with the 5'UTR of the gamma-interferon inducible protein (IP-30) precursor: is this a link between mitochondrial myopathy and inflammation?
abstract: We report the cloning of the genomic and cDNA of the human 51 kDa subunit (NDUFV1) of mitochondrial complex I. The 6 kbp NDUFV1 gene is composed of 10 exons. All intron-exon boundaries comply to the consensus sequence for splice donor and acceptor sites. Within the 5' flanking region we identified a putative binding site for NRF-2, a GATA- and GC-box element. Canonical TATA- or CCAAT-boxes were absent, the transcriptional start site, however, lies within a CpG island, which is consistent with the "housekeeping" function of the gene. Within the coding sequence we detected consensus motifs for NADH, FMN, and iron-sulfur binding sites. The amino acid sequence homology between human and cow is 96.9%. Surprisingly we found a 48 bp long complete antisense homology between the 3'UTR of the NDUFV1-mRNA and the 5'UTR of the mRNA for the gamma-interferon inducible protein precursor (IP-30). This finding is intriguing since both genes lie on different chromosomes. The exact function of IP-30 is not yet known, but it may play a role in gamma-interferon mediated immune reactions. The NDUFV1-mRNA might act as an antisense suppresser, thus restraining translation of IP-30 in tissues with high energy demand. This finding could be a molecular link between complex I deficiency and inflammatory myopathy which have been repeatedly described to occur together.
authors.affiliation: Department of Paediatrics, Nijmegen Center for Mitochondrial Disorders, University Hospital Nijmegen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Schuelke
authors.forename: J
authors.initials: J
authors.lastname: Loeffen
authors.forename: E
authors.initials: E
authors.lastname: Mariman
authors.forename: J
authors.initials: J
authors.lastname: Smeitink
authors.forename: L
authors.initials: L
authors.lastname: van den Heuvel
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D042967:Electron Transport Complex I; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008928:Mitochondria / Q000737:chemistry*; D017240:Mitochondrial Myopathies / Q000235:genetics; D008969:Molecular Sequence Data; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry*; D009245:NADH Dehydrogenase / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; D011506:Proteins / Q000737:chemistry* / Q000502:physiology; D012326:RNA Splicing / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics
chemical_list: D017931:DNA Primers; C112232:NDUFV1 protein, human; D016376:Oligonucleotides, Antisense; D011506:Proteins; D014157:Transcription Factors; D007371:Interferon-gamma; D010088:Oxidoreductases; D016660:NAD(P)H Dehydrogenase (Quinone); D009245:NADH Dehydrogenase; C056859:IFI30 protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors; D042967:Electron Transport Complex I