Albert V R, Lee M R, Bolden A H, Wurzburger R J, Aguanno A
Department of Neuroscience, Roche Institute of Molecular Biology, Nutley, NJ 07110.
Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12053-7. doi: 10.1073/pnas.89.24.12053.
Aromatic L-amino acid decarboxylase (AADC, EC 4.1.1.28) catalyzes the decarboxylation of L-dopa to dopamine in catecholamine cells and 5-hydroxytryptophan to serotonin in serotonin-producing neurons. This enzyme is also expressed in relatively large quantities in nonneuronal tissues such as liver and kidney, where its function is unknown. Neuronal and nonneuronal tissues express AADC mRNAs with distinct 5' untranslated regions. To understand how this is accomplished at the genomic level, we have isolated rat genomic DNA encoding AADC. The organization of the AADC gene suggests that there are two separate promoters specific for the transcription of neuronal and nonneuronal forms of the AADC message. A small exon containing 68 bases of the neuronal-specific 5' end is located approximately 9.5 kilobases upstream of the translation start site, which is contained in the third exon. Approximately 7 kilobases upstream from the neuron-specific promoter is another small exon containing 71 bases of the 5' end of the nonneuronal AADC message. These data suggest that transcription initiating at distinct promoters, followed by alternative splicing, is responsible for the expression of the neuronal and nonneuronal forms of the AADC message.
芳香族L-氨基酸脱羧酶（AADC，EC 4.1.1.28）在儿茶酚胺细胞中催化L-多巴脱羧生成多巴胺，在产生5-羟色胺的神经元中催化5-羟色氨酸脱羧生成5-羟色胺。该酶在肝脏和肾脏等非神经组织中也大量表达，但其功能尚不清楚。神经组织和非神经组织表达的AADC mRNA具有不同的5'非翻译区。为了了解在基因组水平上是如何实现这一点的，我们分离了编码AADC的大鼠基因组DNA。AADC基因的结构表明，存在两个分别特异性启动神经元型和非神经元型AADC信使转录的启动子。一个含有68个碱基的神经元特异性5'端小外显子位于翻译起始位点上游约9.5千碱基处，翻译起始位点包含在第三个外显子中。在神经元特异性启动子上游约7千碱基处是另一个小外显子，含有非神经元型AADC信使5'端的71个碱基。这些数据表明，在不同启动子处起始转录，随后进行可变剪接，是神经元型和非神经元型AADC信使表达的原因。
