Evolutionary analysis reveals regulatory and functional landscape of coding and non-coding RNA editing.
Evolutionary analysis reveals regulatory and functional landscape of coding and non-coding RNA editing.
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进化分析揭示了编码和非编码 RNA 编辑的调控和功能景观。
DOI：
10.1371/journal.pgen.1006563
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发表时间：
2017-02
期刊：
影响因子：
4.5
通讯作者：
Li JB
中科院分区：
文献类型：
--
作者：
Zhang R;Deng P;Jacobson D;Li JB
腺苷到肌苷的RNA编辑使转录组多样化，并促进功能多样性，特别是在大脑中。最近发现了过多的编辑网站；然而，它们是如何被选择和监管的，以及哪些网站具有重要的功能，在很大程度上是未知的。在这里，我们展示了果蝇进化过程中RNA编辑的顺式调控和逐步选择，并精确定位了大量的功能编辑位点。我们发现，果蝇物种编辑的建立和编辑水平的变异在很大程度上是由顺式调控元件解释和预测的。此外，在物种树早期出现的编辑事件往往更多地聚集在一起进行高度编辑，并丰富了缓慢进化的神经元基因，因此表明RNA编辑的主要作用是微调神经功能。虽然非同义编辑事件长期以来一直被认为发挥着功能作用，但除了非同义编辑站点外，很大一部分3‘UTR编辑站点在进化上受到限制，高度编辑，因此可能具有功能。我们发现，这些3‘端非编码区编辑事件可以改变mRNA的稳定性，影响miRNA的结合，从而突出非编码RNA编辑的功能作用。我们的工作，通过对果蝇RNA编辑的进化分析，揭示了RNA编辑调控的新见解以及它在编码区和非编码区的功能。为了微调基因组信息，对RNA进行了许多重要的修改。其中一种类型，腺苷对肌苷(A-to-I)RNA编辑，将某些腺苷改变为肌苷，对许多动物的神经健康是必不可少的。尽管RNA编辑发生在各种动物基因组的数千个位置，但几乎所有编辑事件--特别是非编码区的编辑事件--的功能还没有被研究，决定基因组中特定腺苷是否被编辑的因素也没有得到充分探索。在这里，以果蝇属为模式生物，我们分析了A-to-I RNA编辑的进化，以确定很大一部分编码和非编码编辑事件处于进化限制之下，因此可能具有重要的功能。我们发现，基因3‘端UTRs中的非编码编辑事件可以影响miRNA结合，并与基因表达水平的下降有关。
Adenosine-to-inosine RNA editing diversifies the transcriptome and promotes functional diversity, particularly in the brain. A plethora of editing sites has been recently identified; however, how they are selected and regulated and which are functionally important are largely unknown. Here we show the cis-regulation and stepwise selection of RNA editing during Drosophila evolution and pinpoint a large number of functional editing sites. We found that the establishment of editing and variation in editing levels across Drosophila species are largely explained and predicted by cis-regulatory elements. Furthermore, editing events that arose early in the species tree tend to be more highly edited in clusters and enriched in slowly-evolved neuronal genes, thus suggesting that the main role of RNA editing is for fine-tuning neurological functions. While nonsynonymous editing events have been long recognized as playing a functional role, in addition to nonsynonymous editing sites, a large fraction of 3’UTR editing sites is evolutionarily constrained, highly edited, and thus likely functional. We find that these 3’UTR editing events can alter mRNA stability and affect miRNA binding and thus highlight the functional roles of noncoding RNA editing. Our work, through evolutionary analyses of RNA editing in Drosophila, uncovers novel insights of RNA editing regulation as well as its functions in both coding and non-coding regions. Many important modifications are made to RNA to fine-tune genomic information. One type, Adenosine-to-Inosine (A-to-I) RNA editing, changes certain adenosines to inosines and is essential for the neurological well-being of many animals. Although RNA editing occurs at thousands of sites across the genomes of various animals, the functions of nearly all editing events–particularly those in non-coding regions–have not been studied, and what determines whether particular adenosines across the genome are edited has not been fully explored. Here, using the Drosophila genus as model organisms, we analyze the evolution of A-to-I RNA editing to identify a large fraction of both coding and non-coding editing events that are under evolutionary constraint and therefore likely functionally important. We find that non-coding editing events in the 3’UTRs of genes could affect miRNA binding and are associated with a decrease in gene expression levels.