Hanrahan C J, Palladino M J, Ganetzky B, Reenan R A
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
Genetics. 2000 Jul;155(3):1149-60. doi: 10.1093/genetics/155.3.1149.
Post-transcriptional editing of pre-mRNAs through the action of dsRNA adenosine deaminases results in the modification of particular adenosine (A) residues to inosine (I), which can alter the coding potential of the modified transcripts. We describe here three sites in the para transcript, which encodes the major voltage-activated Na(+) channel polypeptide in Drosophila, where RNA editing occurs. The occurrence of RNA editing at the three sites was found to be developmentally regulated. Editing at two of these sites was also conserved across species between the D. melanogaster and D. virilis. In each case, a highly conserved region was found in the intron downstream of the editing site and this region was shown to be complementary to the region of the exonic editing site. Thus, editing at these sites would appear to involve a mechanism whereby the edited exon forms a base-paired secondary structure with the distant conserved noncoding sequences located in adjacent downstream introns, similar to the mechanism shown for A-to-I RNA editing of mammalian glutamate receptor subunits (GluRs). For the third site, neither RNA editing nor the predicted RNA secondary structures were evolutionarily conserved. Transcripts from transgenic Drosophila expressing a minimal editing site construct for this site were shown to faithfully undergo RNA editing. These results demonstrate that Na(+) channel diversity in Drosophila is increased by RNA editing via a mechanism analogous to that described for transcripts encoding mammalian GluRs.
通过双链RNA腺苷脱氨酶的作用对前体mRNA进行转录后编辑，会导致特定的腺苷（A）残基被修饰为肌苷（I），这可能会改变被修饰转录本的编码潜能。我们在此描述了果蝇中编码主要电压门控性钠（Na⁺）通道多肽的para转录本中的三个位点，RNA编辑在这些位点发生。发现这三个位点的RNA编辑受发育调控。其中两个位点的编辑在黑腹果蝇和粗壮果蝇的物种间也具有保守性。在每种情况下，在编辑位点下游的内含子中都发现了一个高度保守的区域，并且该区域与外显子编辑位点的区域互补。因此，这些位点的编辑似乎涉及一种机制，即被编辑的外显子与位于相邻下游内含子中的远距离保守非编码序列形成碱基配对的二级结构，这类似于哺乳动物谷氨酸受体亚基（GluRs）的A到I RNA编辑所显示的机制。对于第三个位点，RNA编辑和预测的RNA二级结构在进化上均不保守。表达该位点最小编辑位点构建体的转基因果蝇的转录本被证明能如实地进行RNA编辑。这些结果表明，果蝇中的Na⁺通道多样性通过类似于编码哺乳动物GluRs的转录本所描述的机制的RNA编辑而增加。
