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.