Tuning of RNA editing by ADAR is required in Drosophila
Tuning of RNA editing by ADAR is required in Drosophila
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DOI：
10.1038/sj.emboj.7600691
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发表时间：
2005-06-15
期刊：
影响因子：
11.4
通讯作者：
O'Connell, MA
中科院分区：
文献类型：
--
作者：
Keegan, LP;Brindle, J;O'Connell, MA
在果蝇中枢神经系统和肌肉中，编码参与快速突触神经传递的蛋白质的 20 多种转录本的 RNA 编辑在发育过程中增加。仅表达基因组编码的、未经编辑的离子通道亚基亚型的 Adar（作用于 RNA 的腺苷脱氨酶）突变果蝇是可行的，但表现出严重的运动缺陷。 Adar 转录本本身在成年野生型果蝇中进行编辑，以生成靠近 ADAR 活性位点的丝氨酸至甘氨酸取代的同工型。我们表明，编辑限制了 ADAR 功能，因为编辑后的 ADAR 同工型在体外和体内的活性低于基因组编码的、未编辑的同工型。抗编辑的 Adar 转录物在胚胎和幼虫中普遍表达是致命的。该转录本在胚胎肌肉中的表达也是致命的，在编码肌肉电压门控钙通道的转录本位点上具有高于正常、类似成人的编辑水平。
RNA editing increases during development in more than 20 transcripts encoding proteins involved in rapid synaptic neurotransmission in Drosophila central nervous system and muscle. Adar (adenosine deaminase acting on RNA) mutant flies expressing only genome-encoded, unedited isoforms of ion-channel subunits are viable but show severe locomotion defects. The Adar transcript itself is edited in adult wild-type flies to generate an isoform with a serine to glycine substitution close to the ADAR active site. We show that editing restricts ADAR function since the edited isoform of ADAR is less active in vitro and in vivo than the genome-encoded, unedited isoform. Ubiquitous expression in embryos and larvae of an Adar transcript that is resistant to editing is lethal. Expression of this transcript in embryonic muscle is also lethal, with above-normal, adult-like levels of editing at sites in a transcript encoding a muscle voltage-gated calcium channel.