Functional conservation in human and Drosophila of Metazoan ADAR2 involved in RNA editing: loss of ADAR1 in insects.
Functional conservation in human and Drosophila of Metazoan ADAR2 involved in RNA editing: loss of ADAR1 in insects.
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DOI：
10.1093/nar/gkr423
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发表时间：
2011-09-01
影响因子：
14.9
通讯作者：
O'Connell MA
中科院分区：
文献类型：
--
作者：
Keegan LP;McGurk L;Palavicini JP;Brindle J;Paro S;Li X;Rosenthal JJ;O'Connell MA
果蝇Adar基因编码一种RNA编辑酶，参与编辑4%的转录物，携带突变的果蝇有严重的运动缺陷，并发生年龄依赖性神经变性。脊椎动物有两种具有催化活性的adar编辑酶；ADAR1和ADAR2。我们发现人类ADAR2拯救了果蝇Adar突变表型。短核ADAR1p110亚型和较长的干扰素诱导细胞质ADAR1p150亚型都不能有效地修复行走缺陷，也不能正确编辑果蝇转录本中的特定位点。令人惊讶的是，人类ADAR1p110确实抑制果蝇Adar突变体的年龄依赖性神经变性，而ADAR1p150则没有。单个果蝇Adar基因以前被认为代表了多个脊椎动物Adar的进化祖先。人类ADAR2和果蝇ADAR2在功能上的相似性表明它们是真正的同源基因。通过直接克隆和寻找新的无脊椎动物基因组序列的结合，我们发现不同的ADAR1和ADAR2基因在后生动物谱系中很早就存在，都发生在两侧动物和刺胞动物之间的分裂之前。ADAR1基因已经丢失了好几次，包括在昆虫和甲壳类动物的进化过程中。这些数据补充了我们的拯救结果，支持了ADAR1和ADAR2进化出高度保守的、不同的功能的观点。
Flies with mutations in the single Drosophila Adar gene encoding an RNA editing enzyme involved in editing 4% of all transcripts have severe locomotion defects and develop age-dependent neurodegeneration. Vertebrates have two ADAR-editing enzymes that are catalytically active; ADAR1 and ADAR2. We show that human ADAR2 rescues Drosophila Adar mutant phenotypes. Neither the short nuclear ADAR1p110 isoform nor the longer interferon-inducible cytoplasmic ADAR1p150 isoform rescue walking defects efficiently, nor do they correctly edit specific sites in Drosophila transcripts. Surprisingly, human ADAR1p110 does suppress age-dependent neurodegeneration in Drosophila Adar mutants whereas ADAR1p150 does not. The single Drosophila Adar gene was previously assumed to represent an evolutionary ancestor of the multiple vertebrate ADARs. The strong functional similarity of human ADAR2 and Drosophila Adar suggests rather that these are true orthologs. By a combination of direct cloning and searching new invertebrate genome sequences we show that distinct ADAR1 and ADAR2 genes were present very early in the Metazoan lineage, both occurring before the split between the Bilateria and Cnidarians. The ADAR1 gene has been lost several times, including during the evolution of insects and crustacea. These data complement our rescue results, supporting the idea that ADAR1 and ADAR2 have evolved highly conserved, distinct functions.
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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.
影响因子：
11.4
作者：
Keegan, LP;Brindle, J;O'Connell, MA
通讯作者：
O'Connell, MA
影响因子：
4.5
作者：
Palladino, MJ;Keegan, LP;Reenan, RA
通讯作者：
Reenan, RA
影响因子：
16.2
作者：
Greger, IH;Khatri, L;Ziff, EB
通讯作者：
Ziff, EB
影响因子：
16.8
作者：
Bhalla, T;Rosenthal, JJC;Reenan, R
通讯作者：
Reenan, R