Jepson James E C, Reenan Robert A
Department of Molecular Biology, Cell Biology and Biochemistry, SFH Life Sciences Building, Brown University, 185 Meeting Street, Providence, RI 02912, USA.
Biochim Biophys Acta. 2008 Aug;1779(8):459-70. doi: 10.1016/j.bbagrm.2007.11.009. Epub 2007 Dec 3.
Adenosine to inosine RNA editing, catalyzed by Adenosine Deaminases Acting on RNA (ADARs), represents an evolutionary conserved post-transcriptional mechanism which harnesses RNA structures to produce proteins that are not literally encoded in the genome. The species-specific alteration of functionally important residues in a multitude of neuronal ion channels and pre-synaptic proteins through RNA editing has been shown to have profound importance for normal nervous system function in a wide range of invertebrate and vertebrate model organisms. ADARs have also been shown to regulate neuronal gene expression through a remarkable variety of disparate processes, including modulation of the RNAi pathway, the creation of alternative splice sites, and the abolition of stop codons. In addition, ADARs have recently been revealed to have a novel role in the primate lineage: the widespread editing of Alu elements, which comprise approximately 10% of the human genome. Thus, as well as enabling the cell-specific regulation of RNAi and selfish genetic elements, the unshackling of the proteome from the constraints of the genome through RNA editing may have been fundamental to the evolution of complex behavior.
由作用于RNA的腺苷脱氨酶（ADARs）催化的腺苷到肌苷的RNA编辑，是一种进化上保守的转录后机制，它利用RNA结构来产生并非字面上由基因组编码的蛋白质。通过RNA编辑对众多神经元离子通道和突触前蛋白中功能重要残基进行物种特异性改变，已被证明在广泛的无脊椎动物和脊椎动物模型生物中对正常神经系统功能具有深远意义。ADARs还被证明通过多种不同过程调节神经元基因表达，包括对RNAi途径的调节、替代剪接位点的产生以及终止密码子的消除。此外，最近发现ADARs在灵长类谱系中具有新作用：对Alu元件进行广泛编辑，Alu元件约占人类基因组的10%。因此，除了能够对RNAi和自私遗传元件进行细胞特异性调节外，通过RNA编辑使蛋白质组摆脱基因组的限制可能对复杂行为的进化至关重要。
