A newly discovered member of the fatty acid desaturase gene family: A non-coding, antisense RNA gene to Δ5-desaturase
| Autor: | Aaron W. Adamson, Hyekung P. Cho, Chongren Tang, Thomas D. Dreesen, Thomas W. Gettys, Michael Tekle, Steven D. Clarke |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Fatty Acid Desaturases
Male Clinical Biochemistry CHO Cells Rats Sprague-Dawley Mice Open Reading Frames Exon Delta-5 Fatty Acid Desaturase Cricetinae Gene cluster Animals Humans RNA Antisense RNA Messenger Gene Genome biology Intron RNA Cell Biology Animal Feed Molecular biology Rats Antisense RNA Stearoyl-CoA Desaturase Glucose Fatty acid desaturase Liver Biochemistry biology.protein Gene Deletion |
| Zdroj: | Prostaglandins, Leukotrienes and Essential Fatty Acids. 75:97-106 |
| ISSN: | 0952-3278 |
| DOI: | 10.1016/j.plefa.2006.05.001 |
| Popis: | 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 by70%. 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. |
| Databáze: | OpenAIRE |
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