Jepson James E, Reenan Robert A
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.
Fly (Austin). 2010 Apr-Jun;4(2):154-8. doi: 10.4161/fly.4.2.11232. Epub 2010 Apr 17.
In metazoan cells, transcripts that fold into double-strand RNA structures are endowed with the capacity to undergo A-to-I RNA editing, during which adenosines are catalytically deaminated to inosines by a class of enzymes known as ADARs (adenosine deaminases acting on RNA). In Drosophila, a wide range of coding mRNAs associated with signaling in the nervous system undergo A-to-I editing, and loss of editing results in extreme behavioral defects. Furthermore, there are indications that the precursors of endogenous small interfering RNAs also undergo editing. However, the mechanism by which A-to-I editing is related to ethology in Drosophila is unclear, as are the precise cell-types and developmental stages in which editing is most crucial. We have investigated these issues by altering small RNA production in flies lacking ADAR, and modulating editing levels in both time and space through a variety of transgenic techniques. Our results indicate that genetic re-coding in the nervous system is likely to be the primary pathway through which editing affects behavioral outputs, and further suggest that editing is required to 'fine-tune' neuro-transmission in the adult brain.
在多细胞动物细胞中，能够折叠成双链RNA结构的转录本具有进行A-to-I RNA编辑的能力，在此过程中，腺苷被一类称为ADARs（作用于RNA的腺苷脱氨酶）的酶催化脱氨成为肌苷。在果蝇中，大量与神经系统信号传导相关的编码mRNA会发生A-to-I编辑，编辑缺失会导致严重的行为缺陷。此外，有迹象表明内源性小干扰RNA的前体也会经历编辑。然而，A-to-I编辑与果蝇行为学之间的关联机制尚不清楚，编辑最为关键的具体细胞类型和发育阶段也不清楚。我们通过改变缺乏ADAR的果蝇中的小RNA生成，并通过多种转基因技术在时间和空间上调节编辑水平，对这些问题进行了研究。我们的结果表明，神经系统中的基因重新编码可能是编辑影响行为输出的主要途径，并且进一步表明，编辑对于成年大脑中神经传递的“微调”是必需的。
