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大鼠儿茶酚-O-甲基转移酶基因的结构:不同的启动子用于产生该酶可溶性和膜结合形式的mRNA。

Structure of the rat catechol-O-methyltransferase gene: separate promoters are used to produce mRNAs for soluble and membrane-bound forms of the enzyme.

作者信息

Tenhunen J, Salminen M, Jalanko A, Ukkonen S, Ulmanen I

机构信息

Orion-Farmos Pharmaceuticals, Research Center, Helsinki, Finland.

出版信息

DNA Cell Biol. 1993 Apr;12(3):253-63. doi: 10.1089/dna.1993.12.253.

DOI:10.1089/dna.1993.12.253
PMID:8466648
Abstract

The enzyme catechol-O-methyltransferase (COMT) catalyzes the inactivation of catechol-containing molecules by methylation. The cDNAs for the rat and human COMT have recently been cloned and recombinant proteins expressed in prokaryotic and eukaryotic cells. We describe here the structure of the rat COMT gene and its 5'-flanking sequences. The gene spans at least 13 kb and is composed of 5 exons, the first one noncoding. The two ATG codons for the initiation of translation of the membrane-bound (MB-COMT) and soluble (S-COMT) forms of the enzyme reside in the second exon. The gene expresses two mRNA species of 1.6 kb and 1.9 kb that have different tissue distributions. The expression of the transcripts is regulated by at least two promoters, P1 and P2. The P1 promoter expresses the shorter transcript in a tissue-specific manner and is located between the ATG codons in the coding region of the longer transcript. The P2 promoter is constitutive and responsible for the expression of the longer transcript. The shorter 1.6-kb mRNA (S-mRNA) produces only the S-COMT polypeptide, whereas the longer 1.9-kb mRNA (MB-mRNA) is able to direct synthesis of both forms of the COMT enzyme.

摘要

儿茶酚-O-甲基转移酶(COMT)通过甲基化作用催化含儿茶酚分子的失活。大鼠和人类COMT的cDNA最近已被克隆,并在原核和真核细胞中表达了重组蛋白。我们在此描述大鼠COMT基因的结构及其5'侧翼序列。该基因跨度至少13 kb,由5个外显子组成,第一个外显子为非编码区。该酶的膜结合型(MB-COMT)和可溶性型(S-COMT)翻译起始的两个ATG密码子位于第二个外显子中。该基因表达两种长度分别为1.6 kb和1.9 kb的mRNA,它们具有不同的组织分布。转录本的表达受至少两个启动子P1和P2调控。P1启动子以组织特异性方式表达较短的转录本,位于较长转录本编码区的ATG密码子之间。P2启动子是组成型的,负责较长转录本的表达。较短的1.6 kb mRNA(S-mRNA)仅产生S-COMT多肽,而较长的1.9 kb mRNA(MB-mRNA)能够指导合成两种形式的COMT酶。

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