Human RNA-specific adenosine deaminase (ADAR1) gene specifies transcripts that initiate from a constitutively active alternative promoter
Human RNA-specific adenosine deaminase (ADAR1) gene specifies transcripts that initiate from a constitutively active alternative promoter
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DOI：
10.1016/s0378-1119(00)00368-1
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发表时间：
2000-11-27
期刊：
影响因子：
3.5
通讯作者：
Samuel, CE
中科院分区：
文献类型：
--
作者：
Kawakubo, K;Samuel, CE
人ADAR 1基因指定两种大小形式的RNA特异性腺苷脱氨酶，一种干扰素（IFN）诱导型类似于150 kDa蛋白质，一种组成型表达的N-末端截短型类似于110 kDa蛋白质，由不同启动子起始的具有选择性外显子1结构的转录物编码。我们现在已经确定了一类新的ADAR 1转录本，具有替代的5 '-结构和推导的类似于110 kDa蛋白的编码能力。核酸酶保护和cDNA末端的5 '-快速扩增（5'-RACE）揭示了5个主要的ADAR 1转录起始位点，它们定位在先前鉴定的异常大（类似于1.6 kb）的外显子2内。用人羊膜U细胞和胎盘组织的RNA观察这些转录物。它们的丰度不受IFN-α处理培养的U细胞的影响。转染分析确定了人类基因组DNA中的功能性启动子，其映射到ADAR 1基因的近端外显子2区域。启动子活性不受干扰素的影响。这些结果表明，编码组成型表达的类似于110 kDa形式的ADAR 1编辑酶的转录本是从多个启动子启动的，包括外显子2内的一个启动子，这些启动子共同促成了在哺乳动物细胞核中观察到的高基础水平的脱氨酶活性。(C)2000 Elsevier Science B. V.保留所有权利。
The human ADAR1 gene specifies two size forms of RNA-specific adenosine deaminase, an interferon (IFN) inducible similar to 150 kDa protein and a constitutively expressed N-terminally truncated similar to 110 kDa protein, encoded by transcripts with alternative exon 1 structures that initiate from different promoters. We have now identified a new class of ADAR1 transcripts, with alternative 5'-structures and a deduced coding capacity for the similar to 110 kDa protein. Nuclease protection and 5'-rapid amplification of cDNA ends (5'-RACE) revealed five major ADAR1 transcriptional start sites that mapped within the previously identified and unusually large (similar to1.6 kb) exon 2. These transcripts were observed with RNA from human amnion U cells and placenta tissue. Their abundance was not affected by IFN-a treatment of U cells in culture. Transfection analysis identified a functional promoter within human genomic DNA that mapped to the proximal exon 2 region of the ADAR1 gene. Promoter activity was not affected by IFN. These results suggest that transcripts encoding the constitutively expressed similar to 110 kDa form of the ADAR1 editing enzyme are initiated from multiple promoters, including one within exon 2, that collectively contribute to the high basal level of deaminase activity observed in nuclei of mammalian cells. (C) 2000 Elsevier Science B.V. All rights reserved.