A newly discovered member of the fatty acid desaturase gene family: A non-coding, antisense RNA gene to Δ5-desaturase

The rate limiting steps in the conversion of 18-carbon unsaturated fatty acids to 20- and 22-carbon products are catalyzed by two desaturase enzymes (Δ5-desaturase and Δ6-desaturase) found within a lipid desaturase gene cluster. Careful examination of this cluster revealed the existence of a conventionally spliced (human) and an intronless (mouse and rat) non-coding RNA gene, reverse Δ5-desaturase, which is transcribed from the opposite strand of the Δ5-desaturase gene. The 654 bp human reverse Δ5-desaturase transcript contains 269 nucleotides that are complementary to exon 1 and intron 1 of the Δ5-desaturase transcript, and the 3′-end of this sequence contains a 143 nucleotide stretch that is 100% complementary to the 5′-end of the Δ5-desaturase. The rat and mouse transcripts are 1355 and 690 bp long and complementary to a portion of the first intron and the entire first exon of their respective Δ5-desaturases. All reverse Δ5-desaturase transcripts contain several stop codons in all frames suggesting that they do not encode a peptide. Reverse Δ5-desaturase RNA was detected in all rat tissues where Δ5-desaturase is expressed, and the transition between fasting and refeeding produced a significant increase in reverse Δ5-desaturase RNA relative to Δ5-desaturase mRNA. Transient expression of reverse Δ5-desaturase in CHO cells stably transformed with Δ5-desaturase produced a modest decrease in Δ5-desaturase mRNA (30%), but lowered Δ5-desaturase enzymatic activity by >70%. More importantly, a diet enriched in fish oil produced a reciprocal increase in reverse Δ5-desaturase mRNA and decrease in Δ5-desaturase mRNA that was accompanied by a 5–6-fold decrease in Δ5-desaturase enzyme activity. These findings support a significant role for reverse Δ5-desaturase as a natural antisense regulator of Δ5-desaturase.