A newly discovered member of the fatty acid desaturase gene family: a non-coding, antisense RNA gene to delta5-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 (Delta5-desaturase and Delta6-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 Delta5-desaturase, which is transcribed from the opposite strand of the Delta5-desaturase gene. The 654 bp human reverse Delta5-desaturase transcript contains 269 nucleotides that are complementary to exon 1 and intron 1 of the Delta5-desaturase transcript, and the 3'-end of this sequence contains a 143 nucleotide stretch that is 100% complementary to the 5'-end of the Delta5-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 Delta5-desaturases. All reverse Delta5-desaturase transcripts contain several stop codons in all frames suggesting that they do not encode a peptide. Reverse Delta5-desaturase RNA was detected in all rat tissues where Delta5-desaturase is expressed, and the transition between fasting and refeeding produced a significant increase in reverse Delta5-desaturase RNA relative to Delta5-desaturase mRNA. Transient expression of reverse Delta5-desaturase in CHO cells stably transformed with Delta5-desaturase produced a modest decrease in Delta5-desaturase mRNA (30%), but lowered Delta5-desaturase enzymatic activity by >70%. More importantly, a diet enriched in fish oil produced a reciprocal increase in reverse Delta5-desaturase mRNA and decrease in Delta5-desaturase mRNA that was accompanied by a 5-6-fold decrease in Delta5-desaturase enzyme activity. These findings support a significant role for reverse Delta5-desaturase as a natural antisense regulator of Delta5-desaturase.
Dreesen
Thomas D
TD
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.
Adamson
Aaron W
AW
Tekle
Michael
M
Tang
Chongren
C
Cho
Hyekung P
HP
Clarke
Steven D
SD
Gettys
Thomas W
TW
D000821:Animal Feed; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D016678:Genome / Q000235:genetics; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D016366:Open Reading Frames / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000090943:Delta-5 Fatty Acid Desaturase; D016372:RNA, Antisense; D012333:RNA, Messenger; D044943:Fatty Acid Desaturases; D005947:Glucose