Perturbing A-to-I RNA editing using genetics and homologous recombination.

Perturbing A-to-I RNA editing using genetics and homologous recombination.
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使用遗传学和同源重组扰动 A 到 I RNA 编辑。

DOI:
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发表时间:
2011
影响因子:
--
通讯作者:
R. Reenan
R. Reenan
中科院分区:
--
文献类型:
--
作者:
Cynthia Staber;Selena L. Gell;J. Jepson;R. Reenan

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信使RNA(mRNA)中的腺苷转化为肌苷(A-to-I)的证据已经在许多后生动物中发现,特别是那些“最成功”的门:节肢动物门,软体动物门和脊索动物门。A-to-I编辑所必需的酶,ADAR(作用于RNA的腺苷脱氨酶)是高度保守的,并且存在于迄今为止测序的每一个高等后生动物基因组中。果蝇(Drosophila melanogaster)是研究A-to-I编辑的理想模式生物,无论是在基础生物化学方面,还是在确定对生理和行为的适应性下游效应方面。果蝇基因组含有阿达尔的单一结构基因(d阿达尔),但果蝇转录组在编码任何已知生物体的mRNA中具有最广泛的保守和验证的阿达尔靶标。此外,dADAR靶向的许多基因已被遗传鉴定为在神经系统功能中发挥作用,为研究这一有趣过程的生物学相关性提供了丰富的材料来源。在这里,我们讨论了如何在果蝇中使用末端同源重组(HR)的最新进展,使精确控制定义的腺苷残基的编辑状态和工程的苍蝇与全球改变RNA编辑的苍蝇转录组。这些新方法有望显著提高我们对mRNA修饰如何促进昆虫生理学和行为学的理解。
Evidence for the chemical conversion of adenosine-to-inosine (A-to-I) in messenger RNA (mRNA) has been detected in numerous metazoans, especially those "most successful" phyla: Arthropoda, Mollusca, and Chordata. The requisite enzymes for A-to-I editing, ADARs (adenosine deaminases acting on RNA) are highly conserved and are present in every higher metazoan genome sequenced to date. The fruit fly, Drosophila melanogaster, represents an ideal model organism for studying A-to-I editing, both in terms of fundamental biochemistry and in relation to determining adaptive downstream effects on physiology and behavior. The Drosophila genome contains a single structural gene for ADAR (dAdar), yet the fruit fly transcriptome has the widest range of conserved and validated ADAR targets in coding mRNAs of any known organism. In addition, many of the genes targeted by dADAR have been genetically identified as playing a role in nervous system function, providing a rich source of material to investigate the biological relevance of this intriguing process. Here, we discuss how recent advances in the use of ends-out homologous recombination (HR) in Drosophila make possible both the precise control of the editing status for defined adenosine residues and the engineering of flies with globally altered RNA editing of the fly transcriptome. These new approaches promise to significantly improve our understanding of how mRNA modification contributes to insect physiology and ethology.
DOI: --
发表时间: 1996-10
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