dADAR, a Drosophila double-stranded RNA-specific adenosine deaminase is highly developmentally regulated and is itself a target for RNA editing
dADAR, a Drosophila double-stranded RNA-specific adenosine deaminase is highly developmentally regulated and is itself a target for RNA editing
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DOI：
10.1017/s1355838200000248
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发表时间：
2000-07-01
期刊：
影响因子：
4.5
通讯作者：
Reenan, RA
中科院分区：
文献类型：
--
作者：
Palladino, MJ;Keegan, LP;Reenan, RA
我们已经鉴定出果蝇RNA编辑酶的阿达尔（作用于RNA的腺苷脱氨酶）类的同源物，即d阿达尔。dADAR基因座已定位于X染色体的2B 6 -7区域，并在此报告了完整的基因组序列组织。dADAR与哺乳动物RNA编辑酶ADAR 2最同源，ADAR 2是特异性编辑编码谷氨酸受体亚基GluR-B的前体mRNA中的Q/R位点的酶。在巴斯德毕赤酵母中表达的部分纯化的dADAR对合成dsRNA底物具有稳健的非特异性A至I脱氨酶活性。dADAR基因座的转录物来源于两个受调节的启动子。此外，选择性剪接产生至少四种主要的dADAR同种型，其在其氨基末端不同以及改变其dsRNA结合基序之间的间距。dADAR在发育中的神经系统中表达，使其成为作用于中枢神经系统中帕拉电压门控Naf通道转录物的编辑酶的候选物。令人惊讶的是，dADAR本身经历了发育调节的RNA编辑，改变了催化结构域中的保守残基。总之，这些发现表明，dADAR转录本的转录和加工都受到严格的发育控制，并表明果蝇中的RNA编辑过程是动态调节的。
We have identified a homolog of the ADAR (adenosine deaminases that act on RNA) class of RNA editases from Drosophila, dADAR. The dADAR locus has been localized to the 2B6-7 region of the X chromosome and the complete genomic sequence organization is reported here. dADAR is most homologous to the mammalian RNA editing enzyme ADAR2, the enzyme that specifically edits the Q/R site in the pre-mRNA encoding the glutamate receptor subunit GluR-B. Partially purified dADAR expressed in Pichia pastoris has robust nonspecific A-to-I deaminase activity on synthetic dsRNA substrates. Transcripts of the dADAR locus originate from two regulated promoters. In addition, alternative splicing generates at least four major dADAR isoforms that differ at their amino-termini as well as altering the spacing between their dsRNA binding motifs. dADAR is expressed in the developing nervous system, making it a candidate for the editase that acts on para voltage-gated Naf channel transcripts in the central nervous system. Surprisingly, dADAR itself undergoes developmentally regulated RNA editing that changes a conserved residue in the catalytic domain. Taken together, these findings show that both transcription and processing of dADAR transcripts are under strict developmental control and suggest that the process of RNA editing in Drosophila is dynamically regulated.