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大鼠N-乙酰葡糖胺基转移酶I基因的基因组结构和5'-侧翼序列及其转录多样性的调控作用

Genomic structure and 5'-flanking sequences of rat N-acetylglucosaminyltransferase I gene and regulatory role of its transcriptional diversity.

作者信息

Fukada Takashi, Ono Masanobu, Sakata Shohei, Kioka Noriyuki, Sakai Hiroshi, Komano Tohru

机构信息

Laboratory of Applied Molecular Biology, Division of Applied Biochemistry, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, Sakai, Japan.

出版信息

Biosci Biotechnol Biochem. 2003 Jul;67(7):1515-21. doi: 10.1271/bbb.67.1515.

Abstract

It has been known that mouse, rat, and human N-acetylglucosaminyltransferase I (GnT-I) genes produce at least two transcripts, which differ in their 5'-untranslated region (5'-UTR) length, and the longer transcript is preferentially expressed in brains. However, the physiological meaning of this brain-specific expression pattern was unknown. We cloned the rat GnT-I gene and analyzed its structure. It consisted of five exons, and four of them coded only 5'-UTRs. A putative NF-kappaB binding site was found in the 5'-flanking sequence for the transcript that was previously shown to be induced by inflammation. The unusually long 5'-UTR of the major GnT-I transcript in rat brain was shown to inhibit protein production from the following coding sequence in COS7 cells. Comparison of the GnT-I protein/mRNA ratio in rat brain and liver showed that GnT-I mRNA in the brain was translated 3.8-times less efficiently than in the liver. Implications are discussed of these results in regulation of GnT-I expression in rat brain.

摘要

已知小鼠、大鼠和人类的N-乙酰葡糖胺基转移酶I(GnT-I)基因至少产生两种转录本,它们在5'-非翻译区(5'-UTR)长度上有所不同,且较长的转录本在大脑中优先表达。然而,这种大脑特异性表达模式的生理意义尚不清楚。我们克隆了大鼠GnT-I基因并分析了其结构。它由五个外显子组成,其中四个仅编码5'-UTR。在先前显示受炎症诱导的转录本的5'-侧翼序列中发现了一个假定的NF-κB结合位点。大鼠脑中主要GnT-I转录本异常长的5'-UTR在COS7细胞中显示出抑制后续编码序列的蛋白质产生。大鼠脑和肝脏中GnT-I蛋白/ mRNA比率的比较表明,脑中的GnT-I mRNA翻译效率比肝脏低3.8倍。讨论了这些结果对大鼠脑中GnT-I表达调控的影响。

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