Protein recoding by ADAR1-mediated RNA editing is not essential for normal development and homeostasis.
Protein recoding by ADAR1-mediated RNA editing is not essential for normal development and homeostasis.
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DOI：
10.1186/s13059-017-1301-4
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发表时间：
2017-09-05
期刊：
影响因子：
12.3
通讯作者：
Walkley CR
中科院分区：
文献类型：
--
作者：
Heraud-Farlow JE;Chalk AM;Linder SE;Li Q;Taylor S;White JM;Pang L;Liddicoat BJ;Gupte A;Li JB;Walkley CR
通过阿达尔蛋白对dsRNA进行腺苷至肌苷（A至I）编辑是普遍的表位转录组特征。鼠标中定义了数万个A-to-I编辑事件，但大多数事件的功能影响尚不清楚。编辑引起蛋白质重编码是ADAR 2的基本功能，但ADAR 1的重编码的重要作用尚未得到证实。ADAR 1已被提议具有编辑依赖和编辑独立的功能。这些在体内的相对贡献尚未明确界定。ADAR 1的一个关键功能是编辑内源性RNA，以防止激活dsRNA传感器MDA 5（Ifih 1）。除此之外，ADAR 1编辑如何促进正常发育和稳态尚不确定。我们描述了ADAR 1编辑缺陷对小鼠体内平衡的影响。Adar 1 E861 A/E861 A Ifih 1-/-小鼠是惊人的正常，包括他们的寿命。在Adar 1 E861 A/E861 A Ifih 1-/-小鼠中存在轻度、非致病性先天免疫激活特征。评估成人组织中的A-to-I编辑表明，在大脑外部，ADAR 1执行大部分编辑，而ADAR 2无法在其缺失时进行补偿。Adar 1-/-和Adar 1 E861 A/E861 A等位基因的直接比较表明，Ifih 1 +/+和Ifih 1-/-背景具有高度一致性，表明ADAR 1编辑独立功能没有实质性贡献。这些分析表明，在不存在MDA 5的情况下，ADAR 1编辑的终身缺失耐受良好。我们的结论是，由ADAR 1介导的编辑所产生的蛋白质重新编码对于生物体内平衡并不重要。此外，与ADAR 1缺失相关的表型是RNA编辑和MDA 5依赖性功能的结果。本文的在线版本（doi：10.1186/s13059-017-1301-4）包含补充材料，可供授权用户使用。
Adenosine-to-inosine (A-to-I) editing of dsRNA by ADAR proteins is a pervasive epitranscriptome feature. Tens of thousands of A-to-I editing events are defined in the mouse, yet the functional impact of most is unknown. Editing causing protein recoding is the essential function of ADAR2, but an essential role for recoding by ADAR1 has not been demonstrated. ADAR1 has been proposed to have editing-dependent and editing-independent functions. The relative contribution of these in vivo has not been clearly defined. A critical function of ADAR1 is editing of endogenous RNA to prevent activation of the dsRNA sensor MDA5 (Ifih1). Outside of this, how ADAR1 editing contributes to normal development and homeostasis is uncertain. We describe the consequences of ADAR1 editing deficiency on murine homeostasis. Adar1 E861A/E861A Ifih1 -/- mice are strikingly normal, including their lifespan. There is a mild, non-pathogenic innate immune activation signature in the Adar1 E861A/E861A Ifih1 -/- mice. Assessing A-to-I editing across adult tissues demonstrates that outside of the brain, ADAR1 performs the majority of editing and that ADAR2 cannot compensate in its absence. Direct comparison of the Adar1 -/- and Adar1 E861A/E861A alleles demonstrates a high degree of concordance on both Ifih1 +/+ and Ifih1 -/- backgrounds, suggesting no substantial contribution from ADAR1 editing-independent functions. These analyses demonstrate that the lifetime absence of ADAR1-editing is well tolerated in the absence of MDA5. We conclude that protein recoding arising from ADAR1-mediated editing is not essential for organismal homeostasis. Additionally, the phenotypes associated with loss of ADAR1 are the result of RNA editing and MDA5-dependent functions. The online version of this article (doi:10.1186/s13059-017-1301-4) contains supplementary material, which is available to authorized users.
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ADAR1结合的基因组分析及其参与多个RNA处理途径。
影响因子：
16.6
作者：
Bahn, Jae Hoon;Ahn, Jaegyoon;Lin, Xianzhi;Zhang, Qing;Lee, Jae-Hyung;Civelek, Mete;Xiao, Xinshu
通讯作者：
Xiao, Xinshu
DOI：
10.1126/science.aad8711
发表时间：
2016-06-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert WV;Bell TA;Schaening C
通讯作者：
Schaening C
影响因子：
4
作者：
Levanon, Erez Y.;Eisenberg, Eli
通讯作者：
Eisenberg, Eli
ADAR1 通过以催化独立的方式调节 microRNA 加工来实现分化和神经诱导
影响因子：
44.1
作者：
Chen, Tian;Xiang, Jian-Feng;Chen, Ling-Ling
通讯作者：
Chen, Ling-Ling
影响因子：
12.3
作者：
Danecek P;Nellåker C;McIntyre RE;Buendia-Buendia JE;Bumpstead S;Ponting CP;Flint J;Durbin R;Keane TM;Adams DJ
通讯作者：
Adams DJ