Leh H, Chikhi N, Ichino K, Guellaën G, Wellman M, Siest G, Visvikis A
Centre du Médicament, Faculté de Pharmacie UHP Nancy 1, France.
FEBS Lett. 1998 Aug 28;434(1-2):51-6. doi: 10.1016/s0014-5793(98)00950-8.
We have identified and characterized a genomic DNA fragment containing the coding sequences corresponding to the human gamma-glutamyltransferase type 1 mRNA. The coding part of the gene spans over 16 kb and comprises 12 exons and 11 introns exhibiting a similar organization as for the mouse and rat GGT genes. The exons 1-7 encode the heavy subunit whereas exons 8-12 which encode the carboxy-terminal part of the heavy subunit (exon 8) and the light subunit are clustered in a 1.6-kb BglII fragment. Exons 7 and 8 are separated by a 3.9-kb intron containing in its 3' part the sequences corresponding to the 5'-UTRs of the truncated GGT mRNAs described for human lung. Sequence analysis upstream this transcribed region exhibited putative promoter sequences and after transient transfection significant promoter activities were measured in V79 lung fibroblasts and KYN-2 hepatoma cells but not in A2780 ovarian cells. This specificity disappeared when only 550 bp upstream the transcription start site were used as promoter. These results argue for a promoter of truncated GGT mRNAs in intron 7, specifically regulated in human tissues.
我们已经鉴定并表征了一个基因组DNA片段，该片段包含与人类γ-谷氨酰转移酶1型mRNA相对应的编码序列。该基因的编码部分跨度超过16 kb，由12个外显子和11个内含子组成，其组织形式与小鼠和大鼠的GGT基因相似。外显子1-7编码重亚基，而编码重亚基羧基末端部分（外显子8）和轻亚基的外显子8-12聚集在一个1.6 kb的BglII片段中。外显子7和8被一个3.9 kb的内含子隔开，该内含子的3'部分包含与人类肺中描述的截短型GGT mRNA的5'-UTR相对应的序列。该转录区域上游的序列分析显示出推定的启动子序列，瞬时转染后，在V79肺成纤维细胞和KYN-2肝癌细胞中检测到显著的启动子活性，但在A2780卵巢细胞中未检测到。当仅将转录起始位点上游550 bp用作启动子时，这种特异性消失。这些结果表明内含子7中存在截短型GGT mRNA的启动子，其在人类组织中受到特异性调控。
