Rat β-galactoside α2,6-sialyltransferase genomic organization: alternate promoters direct the synthesis of liver and kidney transcripts
Rat β-galactoside α2,6-sialyltransferase genomic organization: alternate promoters direct the synthesis of liver and kidney transcripts
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大鼠β-半乳糖苷α2,6-唾液酸转移酶基因组组织：替代启动子指导肝脏和肾脏转录本的合成
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发表时间：
1990
期刊：
影响因子：
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通讯作者：
J. Lau
中科院分区：
文献类型：
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作者：
Xuecheng Wang;T. O’Hanlon;R. F. Young;J. Lau
大鼠β-半乳糖苷α 2，6-唾液酸转移酶基因被肝脏和肾脏在预测实质上不同多肽的mRNA产生中差异利用。为了确定这些唾液酸转移酶mRNA亚型之间的生物合成关系，分离并分析了基因组序列。跨越至少40 kb DNA的五个外显子携带肝脏β-半乳糖苷α 2，6-唾液酸转移酶蛋白的编码信息。一个额外的外显子仅包含肝脏mRNA的5 '-非翻译前导序列。相比之下，来自该基因的主要肾脏mRNA仅共享三个编码外显子，其指定肝脏唾液酸转移酶蛋白序列的羧基末端42%。此外，这些肾mRNA包含来自其他两个外显子的信息，所述外显子构成这些转录物的5'趋异区。引物延伸和S1核酸酶保护分析表明，肝和肾特异性mRNA的转录起始于唾液酸转移酶基因内的不同位点。虽然肝唾液酸转移酶mRNA从第一外显子转录，但肾转录物从第三内含子内的位点起始。两个转录起始位点上游的基因组区域可以调节细菌氯霉素乙酰转移酶基因在瞬时转染的L细胞中的表达。总之，这些数据暗示多个启动子是唾液酸转移酶表达中肾脏和肝脏基因产物多样性产生的主要机制。
The rat beta-galactoside alpha 2,6-sialytransferase gene is differentially utilized by liver and kidney in the generation of mRNAs that predict substantially divergent polypeptides. In order to determine the biosynthetic relationship between these sialyltransferase mRNA isoforms, genomic sequences were isolated and analysed. Five exons that span at least 40 kb of DNA carry the coding information for the liver beta-galactoside alpha 2,6-sialyltransferase protein. An additional exon contains only sequences for the 5'-untranslated leader of the liver mRNA. In contrast, the predominant kidney mRNAs from this gene share only three coding exons that specify the carboxyl terminal 42% of the liver sialyltransferase protein sequence. In addition, these kidney mRNAs contain information from two other exons that comprise the 5' divergent region of these transcripts. Primer extension and S1 nuclease protection analysis demonstrate that the hepatic and kidney specific mRNAs are transcriptionally initiated at different sites within the sialyltransferase gene. While the hepatic sialyltransferase mRNAs are transcribed from the first exon, the kidney transcripts are initiated from a site within the third intron. Genomic regions upstream of both transcriptional initiation sites can regulate expression of the bacterial chloramphenicol acetyltransferase gene in transiently transfected L cells. Together, the data implicate multiple promoters as a principle mechanism in the generation of kidney and liver gene product diversity in sialyltransferase expression.