Novel putative nicotinic acetylcholine receptor subunit genes, Dalpha5, Dalpha6 and Dalpha7, in Drosophila melanogaster identify a new and highly conserved target of adenosine deaminase acting on RNA-mediated A-to-I pre-mRNA editing.
Novel putative nicotinic acetylcholine receptor subunit genes, Dalpha5, Dalpha6 and Dalpha7, in Drosophila melanogaster identify a new and highly conserved target of adenosine deaminase acting on RNA-mediated A-to-I pre-mRNA editing.
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发表时间：
2002-04
期刊：
影响因子：
3.3
通讯作者：
M. Grauso;R. Reenan;Emmanuel Culetto;D. Sattelle
中科院分区：
文献类型：
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作者：
M. Grauso;R. Reenan;Emmanuel Culetto;D. Sattelle
果蝇的基因组分析揭示了三个新的配体门控离子通道亚基，其特征性YXCC基序仅在α型烟碱乙酰胆碱受体亚基中发现。这些亚基被命名为Dalpha 5、Dalpha 6和Dalpha 7。Dalpha 5胚胎cDNA的克隆揭示了一个巨大的N末端，其中一部分是没有可识别的序列基序，并指定由两个多态性等位基因。来自Dalpha 6的胚胎克隆含有由选择性剪接以及A-to-I前mRNA编辑产生的多种变体转录物。在Dalpha 6中的选择性剪接涉及编码nAChR功能结构域的外显子。Dalpha 6转录物是果蝇腺苷脱氨酶作用于RNA（dADAR）的靶标。这是第一个nAChR基因是mRNA编辑靶点的生物体。7个腺苷可以在Dalpha 6的细胞外配体结合区被修饰，其中4个也在烟草芽夜蛾Heliothis virescens的Dalpha 6直系同源物中被编辑。昆虫目的双翅目和鳞翅目之间的编辑位点的保守性使得nAChR编辑成为迄今为止描述的进化上最保守的无脊椎动物RNA编辑位点。这些发现增加了我们对nAChR亚基多样性的理解，这种多样性是通过基因组和mRNA水平上的机制来增加和调节的。
Genome analysis of the fruit fly Drosophila melanogaster reveals three new ligand-gated ion channel subunits with the characteristic YXCC motif found only in alpha-type nicotinic acetylcholine receptor subunits. The subunits are designated Dalpha5, Dalpha6, and Dalpha7. Cloning of the Dalpha5 embryonic cDNAs reveals an atypically large N terminus, part of which is without identifiable sequence motifs and is specified by two polymorphic alleles. Embryonic clones from Dalpha6 contain multiple variant transcripts arising from alternative splicing as well as A-to-I pre-mRNA editing. Alternative splicing in Dalpha6 involves exons encoding nAChR functional domains. The Dalpha6 transcript is a target of the Drosophila adenosine deaminase acting on RNA (dADAR). This is the first case for any organism where a nAChR gene is the target of mRNA editing. Seven adenosines could be modified in the extracellular ligand-binding region of Dalpha6, four of which are also edited in the Dalpha6 ortholog in the tobacco budworm Heliothis virescens. The conservation of an editing site between the insect orders Diptera and Lepidoptera makes nAChR editing the most evolutionarily conserved invertebrate RNA editing site so far described. These findings add to our understanding of nAChR subunit diversity, which is increased and regulated by mechanisms acting at the genomic and mRNA levels.