Three suppressor mutations which cure a mitochondrial RNA maturase deficiency occur at the same codon in the open reading frame of the nuclear NAM2 gene.

Dominant mutations of the nuclear NAM2 gene are able to compensate for a deficiency of the maturase encoded by the fourth intron of the mitochondrial cytochrome b gene. We have determined the complete nucleotide sequence of the NAM2-1 suppressor allele. The results of S1 nuclease protection experiments show that two overlapping poly(A)+ RNAs are transcribed from the gene using different promoters. The longer transcript contains two open reading frames (ORFs), a long ORF which could encode a protein of 894 amino acids, mol. wt 102,000 daltons, and a short ORF of 51 codons which is omitted from the shorter transcript. The wild-type nam2+ and two other suppressor alleles, NAM2-6 and NAM2-7, have been cloned. A comparison of the sequence of the wild-type and the three suppressor alleles shows that on three separate occasions the same codon specifying glycine was mutated (once to serine and twice to cysteine). Finally sequence comparisons identified two regions in the long ORF, distinct from the position of the suppressor mutations, that could correspond to binding domains for a nucleotide and a nucleic acid.