Palladino M J, Keegan L P, O'Connell M A, Reenan R A
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington 06030, USA.
RNA. 2000 Jul;6(7):1004-18. doi: 10.1017/s1355838200000248.
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 Na+ 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.
我们从果蝇中鉴定出了RNA编辑酶ADAR（作用于RNA的腺苷脱氨酶）家族的一个同源物，即dADAR。dADAR基因座已定位到X染色体的2B6 - 7区域，本文报道了其完整的基因组序列组织。dADAR与哺乳动物RNA编辑酶ADAR2最为同源，ADAR2可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。在毕赤酵母中表达的部分纯化的dADAR对合成双链RNA底物具有强大的非特异性A到I脱氨酶活性。dADAR基因座的转录本源自两个受调控的启动子。此外，可变剪接产生了至少四种主要的dADAR同工型，它们在氨基末端不同，并且改变了其双链RNA结合基序之间的间距。dADAR在发育中的神经系统中表达，这使其成为作用于中枢神经系统中对电压门控钠通道转录本进行编辑的酶的候选者。令人惊讶的是，dADAR自身也经历了发育调控的RNA编辑，该编辑改变了催化结构域中的一个保守残基。综上所述，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编辑过程是动态调控的。
