Phylogenetic conservation of the makorin-2 gene, encoding a multiple zinc-finger protein, antisense to the RAF1 proto-oncogene

Natural endogenous antisense RNAs have been reported in multiple loci, with evidence in some cases supporting a regulatory role for the antisense tran script. Here, we describe a novel gene, makorin RING zinc finger-2 (MKRN2), that overlaps and is antisense to the gene RAF1 in mammals. Phylogenetic a nalysis of the 3' untranslated region of RAF1 orthologues suggests that thi s relationship may have existed for up to 450 million years. We have also i dentified MKRN2 orthologues in two species of fish. This places the gene du plication event that created this locus from an ancestral MKRN1 gene early in vertebrate evolution, over 450 million years ago. Northern blot analyses show that human MKRN2 and RAF1 are co-expressed in tissues and cell lines, raising the possibility of mRNA duplex formation. The encoded makorin-2 pr otein is likely a ribonucleoprotein of unknown function, but its conservati on suggests an important cellular role. The data presented here describe a conserved vertebrate MKRN2 gene that is closely associated with the RAF1 lo cus.