Roy R, Taourit S, Zaragoza P, Eggen A, Rodellar C
Laboratorio de Genética Bioquímica y Grupos Sanguíneos, Universidad de Zaragoza, Zaragoza, Spain.
Cytogenet Genome Res. 2005;111(1):65-73. doi: 10.1159/000085672.
Fatty acid synthesis differs considerably between monogastric and ruminant species. Fatty acid synthase (FASN) plays a central role in de novo lipogenesis in mammals. FASN has seven active sites which help to catalyse all the reaction steps in the conversion of acetyl-CoA and malonyl-CoA to palmitate. In this work, the bovine fatty acid synthase gene (FASN) was cloned, characterized and compared to the human and rat orthologs. Comparative analysis reveals evolutionarily conserved exon regions and gene flanking sequences. Analysis of the DNA sequence in the 5' flanking region of the FASN bovine gene revealed a potential TATA box, CAAT box and 5 Sp1 binding sites located in a CpG island. RT-PCR and Western blot analysis showed that FASN expression was higher in brain, testis and adipose tissue than in liver and heart. The longer form of the FASN cDNA includes a 7,542-bp sequence which encodes a protein with 2,513 amino acids. An alternative transcript was discovered in bovine and ovine tissues devoid of part of exon 9. The removal of part of exon 9 by post-transcriptional splicing causes a frameshift in the open reading frame and results in a premature termination codon. We hypothesize that in ruminants, FASN may be regulated by the ratio between the two transcripts. The small transcript is mostly produced in tissues with low fatty acid synthesis.
单胃动物和反刍动物的脂肪酸合成有很大差异。脂肪酸合酶（FASN）在哺乳动物的从头脂肪生成中起核心作用。FASN有七个活性位点，有助于催化乙酰辅酶A和丙二酰辅酶A转化为棕榈酸酯的所有反应步骤。在这项工作中，克隆了牛脂肪酸合酶基因（FASN），对其进行了表征，并与人类和大鼠的直系同源基因进行了比较。比较分析揭示了进化上保守的外显子区域和基因侧翼序列。对牛FASN基因5'侧翼区域的DNA序列分析显示，在一个CpG岛中存在一个潜在的TATA盒、CAAT盒和5个Sp1结合位点。RT-PCR和蛋白质印迹分析表明，FASN在脑、睾丸和脂肪组织中的表达高于肝脏和心脏。FASN cDNA的较长形式包含一个7542 bp的序列，编码一个含有2513个氨基酸的蛋白质。在牛和羊的组织中发现了一种缺失部分外显子9的可变转录本。转录后剪接去除部分外显子9会导致开放阅读框移码，并产生一个提前终止密码子。我们推测，在反刍动物中，FASN可能受这两种转录本比例的调节。小转录本主要在脂肪酸合成较低的组织中产生。
