George Cyril X, Das Sonali, Samuel Charles E
Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
Virology. 2008 Oct 25;380(2):338-43. doi: 10.1016/j.virol.2008.07.029. Epub 2008 Sep 6.
The p150 form of the RNA-specific adenosine deaminase ADAR1 is interferon-inducible and catalyzes A-to-I editing of viral and cellular RNAs. We have characterized mouse genomic clones containing the promoter regions required for Adar1 gene transcription and analyzed interferon induction of the p150 protein using mutant mouse cell lines. Transient transfection analyses using reporter constructs led to the identification of three promoters, one interferon-inducible (P(A)) and two constitutively active (P(B) and P(C)). The TATA-less P(A) promoter, characterized by the presence of a consensus ISRE element and a PKR kinase KCS-like element, directed interferon-inducible reporter expression in rodent and human cells. Interferon induction of p150 was impaired in mouse cells deficient in IFNAR receptor, JAK1 kinase or STAT2 but not STAT1. Whereas Adar1 gene organization involving multiple promoters and alternative exon 1 structures was highly preserved, sequences of the promoters and exon 1 structures were not well conserved between human and mouse.
RNA特异性腺苷脱氨酶ADAR1的p150形式可被干扰素诱导，并催化病毒和细胞RNA的A到I编辑。我们对包含Adar1基因转录所需启动子区域的小鼠基因组克隆进行了表征，并使用突变小鼠细胞系分析了p150蛋白的干扰素诱导情况。使用报告基因构建体进行的瞬时转染分析鉴定出了三个启动子，一个可被干扰素诱导（P(A)），两个组成型活性启动子（P(B)和P(C)）。无TATA的P(A)启动子的特征是存在一个共有ISRE元件和一个PKR激酶KCS样元件，可在啮齿动物和人类细胞中指导干扰素诱导的报告基因表达。在缺乏IFNAR受体、JAK1激酶或STAT2但不缺乏STAT1的小鼠细胞中，p150的干扰素诱导受损。虽然涉及多个启动子和可变外显子1结构的Adar1基因组织高度保守，但人和小鼠之间启动子序列和外显子1结构并不保守。
