Structural analysis of the genes for human arylamine N-acetyltransferases and characterisation of alternative transcripts
Structural analysis of the genes for human arylamine N-acetyltransferases and characterisation of alternative transcripts
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DOI：
10.1111/j.1742-7843.2005.pto_02.x
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发表时间：
2005-05-01
影响因子：
3.1
通讯作者：
Sim, E
中科院分区：
文献类型：
--
作者：
Boukouvala, S;Sim, E
芳胺n -乙酰转移酶是多态药物代谢酶。人类同种异构体NAT1和NAT2由两个具有无内含子编码区的基因编码。与主要存在于肠道和肝脏的NAT2不同，人类NAT1蛋白存在于许多组织中。我们通过分析基因组数据库的数据，描述了人类NAT基因的外显子-内含子结构。将NAT基因序列与人类8号染色体序列进行比较，发现在NAT1基因单编码外显子上游51.5、51.4、12.3、11.9、10.8、9.6、5.2和2.6 kb处存在8个非编码外显子。许多表达的序列标签也表明转录起始来自NAT1编码外显子附近的上游区域，与早期研究一致。NAT2基因由一个先前的。描述了非编码外显子和一个编码外显子，间隔8.6 KB。利用心脏、大脑、胎盘、肺、肝、骨骼肌、肾脏和胰腺的cDNA， RT - PCR也证实了这些发现。在所有组织中均发现了选择性剪接的NAT1转录本。在这些组织中也检测到NAT2基因的转录，并被证明从非编码外显子开始或从编码外显子的上游开始。RT - PCR产物的比较提供了在每个组织中表达的不同NAT转录物的相对量的初步估计。最后，表达序列标签分析和RTPCR均表明，NAT1和NAT2存在两种不同利用的聚腺苷化信号，分别位于每个基因编码区下游约0.2和0.3 kb处。
Arylamine N-acetyltransferases are polymorphic drug-metabolising enzymes. The human isoforms, NAT1 and NAT2, are encoded by two genes with intronless coding regions. Human NAT1 protein is found in many tissues, unlike NAT2 which is present predominantly in the intestine and liver. We describe the exon-intron structure of the human NAT genes by analysing data from genomic databases. Comparison of expressed sequence tags, matching NAT gene sequences, with the sequence of human chromosome 8 implied the presence of 8 non-coding exons located 51.5, 51.4, 12.3, 11.9, 10.8, 9.6, 5.2 and 2.6 kb upstream of the single coding exon of the NAT1 gene. A number of expressed sequence tags also indicated transcription initiation from the upstream region adjacent to the NAT1 coding exon, consistent with earlier studies. The NAT2 gene consists of one previously. described non-coding and one coding exon, located 8.6 kb apart. These findings were also confirmed by RT PCR, using cDNA from heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Alternatively spliced NAT1 transcripts were found in all tissues. Transcription of the NAT2 gene was also detected in these tissues and was demonstrated to start either from the non-coding exon or from immediately upstream of the coding exon. Comparison of the RT PCR products provided an initial estimate of the relative amounts of the different NAT transcripts expressed in each tissue. Finally, both expressed sequence tag analysis and RTPCR demonstrated the presence of two differentially utilised polyadenylation signals for NAT1 and NAT2, located about 0.2 and 0.3 kb downstream of the coding region of each gene.