title: A novel FADS1 isoform potentiates FADS2-mediated production of eicosanoid precursor fatty acids.
abstract: The fatty acid desaturase (FADS) genes code for the rate-limiting enzymes required for the biosynthesis of long-chain polyunsaturated fatty acids (LCPUFA). Here we report discovery and function of a novel FADS1 splice variant. FADS1 alternative transcript 1 (FADS1AT1) enhances desaturation of FADS2, leading to increased production of eicosanoid precursors, the first case of an isoform modulating the enzymatic activity encoded by another gene. Multiple protein isoforms were detected in primate liver, thymus, and brain. In human neuronal cells, their expression patterns are modulated by differentiation and result in alteration of cellular fatty acids. FADS1, but not FADS1AT1, localizes to endoplasmic reticulum and mitochondria. Ribosomal footprinting demonstrates that all three FADS genes are translated at similar levels. The noncatalytic regulation of FADS2 desaturation by FADS1AT1 is a novel, plausible mechanism by which several phylogenetically conserved FADS isoforms may regulate LCPUFA biosynthesis in a manner specific to tissue, organelle, and developmental stage.
authors.affiliation: Division of Nutritional Sciences,  Cornell University, Ithaca, NY.
authors.forename: Woo Jung
authors.initials: WJ
authors.lastname: Park
authors.forename: Kumar S D
authors.initials: KS
authors.lastname: Kothapalli
authors.forename: Holly T
authors.initials: HT
authors.lastname: Reardon
authors.forename: Peter
authors.initials: P
authors.lastname: Lawrence
authors.forename: Shu-Bing
authors.initials: SB
authors.lastname: Qian
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Brenna
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019295:Computational Biology; D000090943:Delta-5 Fatty Acid Desaturase; D015777:Eicosanoids / Q000096:biosynthesis*; D004622:Embryo, Mammalian / Q000166:cytology; D005091:Exons / Q000235:genetics; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D010215:Papio; D011061:Poly A / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D015777:Eicosanoids; D007527:Isoenzymes; D012333:RNA, Messenger; D011061:Poly A; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; C533241:FADS2 protein, human