Dynamic response of RNA editing to temperature in Drosophila.
Dynamic response of RNA editing to temperature in Drosophila.
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DOI：
10.1186/s12915-014-0111-3
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发表时间：
2015-01-03
期刊：
影响因子：
5.4
通讯作者：
Reenan RA
中科院分区：
文献类型：
--
作者：
Rieder LE;Savva YA;Reyna MA;Chang YJ;Dorsky JS;Rezaei A;Reenan RA
腺苷到肌苷RNA编辑是一个高度保守的过程，其在转录后修饰mRNA，产生蛋白质组多样性，特别是在后生动物的神经系统内。编码参与神经传递的蛋白质的转录物作为这种修饰的靶占主导地位。先前的报告表明，RNA编辑对温度变化形式的环境输入做出反应。然而，温度依赖性RNA编辑反应背后的分子决定因素还没有得到很好的理解。使用变温果蝇，我们表明，在正常生理范围内的急性温度变化导致RNA编辑水平的实质性变化。我们对特定位点的研究揭示了编辑对温度反应的模式的多样性，这些模式在代表超过1000万年分歧的五种果蝇中是保守的。此外，我们表明，编辑酶，阿达尔（腺苷脱氨酶作用于RNA）的表达，显着降低在高温下，部分，但不完全，解释了一些目标的温度响应。有趣的是，在升高的温度下编辑酶水平的这种降低仅通过返回到较低的温度而部分逆转。最后，我们表明，在钠通道转录本中，最温度敏感的编辑位点的工程结构变体扰乱了特定RNA结构的RNA编辑谱中的热响应性。我们的研究结果表明，RNA编辑过程通过两种不同的分子机制对温度变化做出反应：通过指导编辑的RNA结构的固有热敏性，以及由于RNA编辑酶的温度敏感性表达或稳定性。环境因素，在这种情况下，温度，通过RNA编辑快速重新编程果蝇转录组，可能导致编辑和未编辑蛋白质的蛋白质组比例改变。本文的在线版本（doi：10.1186/s12915-014-0111-3）包含补充材料，可供授权用户使用。
Adenosine-to-inosine RNA editing is a highly conserved process that post-transcriptionally modifies mRNA, generating proteomic diversity, particularly within the nervous system of metazoans. Transcripts encoding proteins involved in neurotransmission predominate as targets of such modifications. Previous reports suggest that RNA editing is responsive to environmental inputs in the form of temperature alterations. However, the molecular determinants underlying temperature-dependent RNA editing responses are not well understood. Using the poikilotherm Drosophila, we show that acute temperature alterations within a normal physiological range result in substantial changes in RNA editing levels. Our examination of particular sites reveals diversity in the patterns with which editing responds to temperature, and these patterns are conserved across five species of Drosophilidae representing over 10 million years of divergence. In addition, we show that expression of the editing enzyme, ADAR (adenosine deaminase acting on RNA), is dramatically decreased at elevated temperatures, partially, but not fully, explaining some target responses to temperature. Interestingly, this reduction in editing enzyme levels at elevated temperature is only partially reversed by a return to lower temperatures. Lastly, we show that engineered structural variants of the most temperature-sensitive editing site, in a sodium channel transcript, perturb thermal responsiveness in RNA editing profile for a particular RNA structure. Our results suggest that the RNA editing process responds to temperature alterations via two distinct molecular mechanisms: through intrinsic thermo-sensitivity of the RNA structures that direct editing, and due to temperature sensitive expression or stability of the RNA editing enzyme. Environmental cues, in this case temperature, rapidly reprogram the Drosophila transcriptome through RNA editing, presumably resulting in altered proteomic ratios of edited and unedited proteins. The online version of this article (doi:10.1186/s12915-014-0111-3) contains supplementary material, which is available to authorized users.
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影响因子：
11.4
作者：
Heale, Bret S. E.;Keegan, Liam P.;McGurk, Leeanne;Michlewski, Gracjan;Brindle, James;Stanton, Chloe M.;Caceres, Javier F.;O'Connell, Mary A.
通讯作者：
O'Connell, Mary A.
识别广泛的超编辑人类RNA。
影响因子：
4.5
作者：
Carmi S;Borukhov I;Levanon EY
通讯作者：
Levanon EY
影响因子：
12.3
作者：
Pinto Y;Cohen HY;Levanon EY
通讯作者：
Levanon EY
DOI：
10.1126/science.1212795
发表时间：
2012-02-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Garrett S;Rosenthal JJ
通讯作者：
Rosenthal JJ
影响因子：
2.8
作者：
Hoffmann, A. A.
通讯作者：
Hoffmann, A. A.