State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China.
Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3769-74. doi: 10.1073/pnas.1321745111. Epub 2014 Feb 24.
Impairment of RNA editing at a handful of coding sites causes severe disorders, prompting the view that coding RNA editing is highly advantageous. Recent genomic studies have expanded the list of human coding RNA editing sites by more than 100 times, raising the question of how common advantageous RNA editing is. Analyzing 1,783 human coding A-to-G editing sites, we show that both the frequency and level of RNA editing decrease as the importance of a site or gene increases; that during evolution, edited As are more likely than unedited As to be replaced with Gs but not with Ts or Cs; and that among nonsynonymously edited As, those that are evolutionarily least conserved exhibit the highest editing levels. These and other observations reveal the overall nonadaptive nature of coding RNA editing, despite the presence of a few sites in which editing is clearly beneficial. We propose that most observed coding RNA editing results from tolerable promiscuous targeting by RNA editing enzymes, the original physiological functions of which remain elusive.
在少数几个编码位点的 RNA 编辑功能受损会导致严重的疾病，这促使人们认为编码 RNA 编辑具有高度优势。最近的基因组研究将人类编码 RNA 编辑位点的数量增加了 100 多倍，这就提出了一个问题，即有利的 RNA 编辑有多普遍。通过分析 1783 个人类编码 A 到 G 的编辑位点，我们发现，随着一个位点或基因重要性的增加，RNA 编辑的频率和水平都会降低；在进化过程中，编辑过的 As 比未编辑的 As 更有可能被替换为 Gs，而不是 Ts 或 Cs；在非同义编辑的 As 中，进化上最不保守的 As 表现出最高的编辑水平。这些和其他观察结果揭示了编码 RNA 编辑的总体非适应性，尽管存在少数几个明显有利的编辑位点。我们提出，大多数观察到的编码 RNA 编辑是由 RNA 编辑酶的可容忍的混杂靶向引起的，而这些酶的原始生理功能仍然难以捉摸。
