Mammalian conserved ADAR targets comprise only a small fragment of the human editosome.
Mammalian conserved ADAR targets comprise only a small fragment of the human editosome.
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DOI：
10.1186/gb-2014-15-1-r5
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发表时间：
2014-01-07
期刊：
影响因子：
12.3
通讯作者：
Levanon EY
中科院分区：
文献类型：
--
作者：
Pinto Y;Cohen HY;Levanon EY
阿达尔蛋白是研究最广泛的RNA结合蛋白之一。它们与靶点结合并将特定的腺苷脱氨为肌苷。阿达尔活性是必不可少的，并且编辑其靶标的子集对于生存力至关重要。最近，通过分析下一代测序数据检测到大量新的阿达尔靶标。这些新的编辑位点大多位于谱系特异性基因组重复序列中，这可能是编辑酶过度活性的结果，从而掩盖了功能位点。在这项研究中，我们的目标是确定一套哺乳动物保守的阿达尔的目标。我们使用来自人、小鼠、大鼠、牛、负鼠和鸭嘴兽的RNA测序数据来定义保守的哺乳动物阿达尔靶点集。我们发现，保守的哺乳动物编辑位点数量惊人地少，并且具有独特的特征，将它们与非保守的编辑位点区分开来。构成该组的位点具有独特的基因组分布，倾向于位于编码神经递质受体或其他突触相关蛋白的基因中，并且具有更高的编辑和表达水平。我们还发现小鼠品系内以及人和小鼠之间的这组编辑水平的高度一致性。在这些位点中编辑的严格调控跨菌株和物种暗示了它们的功能重要性。尽管发现了许多编辑靶点，但只有少数在哺乳动物进化中是保守的。这些位点是高度保守的，并表现出独特的功能，如严格的监管，并可能在哺乳动物生物学中发挥关键作用。
ADAR proteins are among the most extensively studied RNA binding proteins. They bind to their target and deaminate specific adenosines to inosines. ADAR activity is essential, and the editing of a subset of their targets is critical for viability. Recently, a huge number of novel ADAR targets were detected by analyzing next generation sequencing data. Most of these novel editing sites are located in lineage-specific genomic repeats, probably a result of overactivity of editing enzymes, thus masking the functional sites. In this study we aim to identify the set of mammalian conserved ADAR targets. We used RNA sequencing data from human, mouse, rat, cow, opossum, and platypus to define the conserved mammalian set of ADAR targets. We found that the conserved mammalian editing sites are surprisingly small in number and have unique characteristics that distinguish them from non-conserved ones. The sites that constitute the set have a distinct genomic distribution, tend to be located in genes encoding neurotransmitter receptors or other synapse related proteins, and have higher editing and expression levels. We also found a high consistency of editing levels of this set within mice strains and between human and mouse. Tight regulation of editing in these sites across strains and species implies their functional importance. Despite the discovery of numerous editing targets, only a small number of them are conserved within mammalian evolution. These sites are extremely highly conserved and exhibit unique features, such as tight regulation, and probably play a pivotal role in mammalian biology.
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影响因子：
4.4
作者：
Greenberger S;Levanon EY;Paz-Yaacov N;Barzilai A;Safran M;Osenberg S;Amariglio N;Rechavi G;Eisenberg E
通讯作者：
Eisenberg E
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：
16.8
作者：
Bhalla, T;Rosenthal, JJC;Reenan, R
通讯作者：
Reenan, R
影响因子：
56.9
作者：
Hoopengardner, B;Bhalla, T;Reenan, R
通讯作者：
Reenan, R
影响因子：
64.8
作者：
Graveley BR;Brooks AN;Carlson JW;Duff MO;Landolin JM;Yang L;Artieri CG;van Baren MJ;Boley N;Booth BW;Brown JB;Cherbas L;Davis CA;Dobin A;Li R;Lin W;Malone JH;Mattiuzzo NR;Miller D;Sturgill D;Tuch BB;Zaleski C;Zhang D;Blanchette M;Dudoit S;Eads B;Green RE;Hammonds A;Jiang L;Kapranov P;Langton L;Perrimon N;Sandler JE;Wan KH;Willingham A;Zhang Y;Zou Y;Andrews J;Bickel PJ;Brenner SE;Brent MR;Cherbas P;Gingeras TR;Hoskins RA;Kaufman TC;Oliver B;Celniker SE
通讯作者：
Celniker SE