Role of the Defective Splicing of mRNA in the Lack of Pulmonary Expression of Constitutively Active Receptor in Rat
Role of the Defective Splicing of mRNA in the Lack of Pulmonary Expression of Constitutively Active Receptor in Rat
复制标题
mRNA 剪接缺陷在大鼠肺组成型活性受体表达缺失中的作用
DOI：
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Y. Inouye
中科院分区：
文献类型：
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作者：
Yuichiro Kanno;S. Aoki;T. Nakahama;Y. Inouye
哺乳动物组成型活性受体（CAR）是一种配体激活的转录因子，以器官特异性方式参与控制细胞色素P450 2B（CYP 2B）基因对外源性物质的反应。在存在苯巴比妥（PB）或PB型药物的情况下，肝脏CYP 2B形式具有高度诱导性。相反，在肺中很少观察到CYP 2B活性表达的PB依赖性增加。RT-PCR检测到7周龄Wistar大鼠肝脏中有成熟的CAR mRNA，而肺中的CAR mRNA在肝脏CAR mRNA的编码区插入了91 bp的额外核苷酸序列。通过比较肝CAR mRNA的全长序列，包括5′-和3′-非翻译区（3′-UTR），与本研究中完成的基因组序列，阐明了基因组结构由9个外显子和8个内含子组成，其中，编码区从外显子2的5′端附近延伸至外显子9的前1/3，在最常获得的cDNA克隆中的UTR。在肺CAR mRNA中，内含子6没有被剪接掉，这意味着肺中CAR的缺乏可能部分是由于前体mRNA在其成熟过程中的不完全剪接。
The mammalian constitutively active receptor (CAR) is a ligand-activated transcription factor that participates in controlling the expression of cytochrome P450 2B (CYP2B) genes in response to xenobiotics in an organ-specific manner. In the presence of phenobarbital (PB) or PB-type agents, hepatic CYP2B forms are highly inducible. In contrast, PB-dependent increases in the expression of CYP2B activities are rarely observed in the lung. Mature CAR mRNA could be detected in the liver of 7-week-old Wistar rats by RT-PCR, while lung CAR mRNA had a 91 bp extra nucleotide sequence inserted in a coding region of hepatic CAR mRNA. By comparing the full- length sequence of hepatic CAR mRNA, including 5′- and 3′-untranslated region (3′-UTR), with the genomic sequence completed in the present study, the genomic structure was clarified to consist of 9 exons and 8 introns, in which the coding region expanded from exon 2 in close to its 5′-end to the first one-third of exon 9 after 159 bp of 5′-UTR in the most frequently obtained cDNA clones. In pulmonary CAR mRNA, intron 6 was not spliced out, implying that the lack of CAR in the lung might in part result from the incomplete splicing of precursor mRNA during its maturation.
核受体 CAR 作为苯巴比妥在大鼠肝脏中诱导 CYB2B1 基因性二态性的调节因子。
影响因子：
3.6
作者：
Yoshinari,K;Sueyoshi,T;Moore,R;Negishi,M
通讯作者：
Negishi,M