ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins.
ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins.
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DOI：
10.1093/nar/gkw1304
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发表时间：
2017-04-20
影响因子：
14.9
通讯作者：
Prasanth KV
中科院分区：
文献类型：
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作者：
Anantharaman A;Tripathi V;Khan A;Yoon JH;Singh DK;Gholamalamdari O;Guang S;Ohlson J;Wahlstedt H;Öhman M;Jantsch MF;Conrad NK;Ma J;Gorospe M;Prasanth SG;Prasanth KV
作用于RNA的腺苷脱氨酶（ADARs）催化RNA序列中腺苷残基编辑为肌苷（A-to-I），主要是在内含子和utr（非翻译区）中。在RNA的非编码区域内进行编辑的意义尚不清楚。在这里，我们证明了ADAR2与RNA的关联稳定了转录本的一个子集。ADAR2与细胞核保留的Cat2转录核RNA （Ctn RNA）相互作用并编辑3΄UTR。在ADAR2缺失的情况下，Ctn RNA的丰度和半衰期明显降低。此外，adar2介导的Ctn RNA稳定以编辑无关的方式发生。未编辑的Ctn RNA显示出与RNA结合蛋白HuR和PARN[聚(A)特异性核糖核酸酶去烯化酶]的增强相互作用。在没有ADAR2的情况下，HuR和PARN使Ctn RNA不稳定，表明ADAR2通过拮抗PARN和HuR对Ctn RNA的降解来稳定Ctn RNA。转录组学分析确定了其他受类似机制调节的rna。总之，我们确定了一种调节机制，其中ADAR2通过限制RNA不稳定蛋白与其同源底物的相互作用来增强靶RNA的稳定性。
Adenosine deaminases acting on RNA (ADARs) catalyze the editing of adenosine residues to inosine (A-to-I) within RNA sequences, mostly in the introns and UTRs (un-translated regions). The significance of editing within non-coding regions of RNA is poorly understood. Here, we demonstrate that association of ADAR2 with RNA stabilizes a subset of transcripts. ADAR2 interacts with and edits the 3΄UTR of nuclear-retained Cat2 transcribed nuclear RNA (Ctn RNA). In absence of ADAR2, the abundance and half-life of Ctn RNA are significantly reduced. Furthermore, ADAR2-mediated stabilization of Ctn RNA occurred in an editing-independent manner. Unedited Ctn RNA shows enhanced interaction with the RNA-binding proteins HuR and PARN [Poly(A) specific ribonuclease deadenylase]. HuR and PARN destabilize Ctn RNA in absence of ADAR2, indicating that ADAR2 stabilizes Ctn RNA by antagonizing its degradation by PARN and HuR. Transcriptomic analysis identified other RNAs that are regulated by a similar mechanism. In summary, we identify a regulatory mechanism whereby ADAR2 enhances target RNA stability by limiting the interaction of RNA-destabilizing proteins with their cognate substrates.