CLONING OF THE HUMAN MITOCHONDRIAL 51 KDA SUBUNIT (NDUFV1) REVEALS A 100-PERCENT 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

We report the cloning of the genomic and cDNA of the human 51 kDa subu nit (NDUFV1) of mitochondrial complex I. The 6 kbp NDUFV1 gene is comp osed of 10 exons. AU intron-exon boundaries comply to the con sensus s equence for splice donor and acceptor sites. Within the 5' flanking re gion we identified a putative binding site for NRF-2, a GATA- and CC-b ox element. Canonical TATA-or CCAAT-boxes were absent, the transcripti onal start site, however, lies within a CpG island, which is consisten t with the ''housekeeping'' function of the gene. Within the coding se quence we detected consensus motifs for NADH, FMN, and iron-sulfur bin ding 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 f unction of IP-30 is not yet known, but it may play a role in gamma-int erferon mediated immune reactions, The NDUFV1-mRNA might act as an ant isense suppresser, thus restraining translation of IP-30 in tissues wi th high energy demand. This finding could be a molecular link between complex I deficiency and inflammatory myopathy which have been repeate dly described to Occur together. (C) 1998 Academic Press.