文章基本信息

标题：A novel FADS1 isoform potentiates FADS2-mediated production of eicosanoid precursor fatty acids
本地全文：下载
作者：Woo Jung Park ; Kumar S. D. Kothapalli ; Holly T. Reardon 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2012
卷号：53
期号：8
页码：1502-1512
DOI：10.1194/jlr.M025312
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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.
关键词：alternative splicing ; arachidonic acid ; fatty acid desaturases ; fatty acid biosynthesis ; gene expression