mRNA Editing: A to I Conversion

In humans the deamination of adenosines to inosines is the most common editing event. It is particularly prevalent in the brain, where it leads to amino acid changes that affect the conductance of several ion channels. Inosines are recognized by the translation machinery as if they were guanosines.<BR>ADARs (Adenosine Deaminases Acting on RNA) modify pre-mRNA, acting as single peptides and recognize structural determinants in the RNA. To date 3 members of this deaminase family are known: ADAR 1, ADAR 2, and ADAR 3 that share a common modular domain structure. ADAR 1 and 2 contain a catalytic deaminase domain, a double-stranded RNA binding domain and exhibit RNA editing activity. ADAR1 activity is found in various mammalian tissues with the highest concentration in brain.<BR>An increasing number of mammalian genes have been found to undergo deamination by ADARs. Deamination by editing in pre-mRNAs encoding subunits of ionotropic glutamate receptors (GluRs) is another well studied example. An editing event at the Q/R site of the GluR2 (GluRB) subunit of AMPA receptors converts a Gln codon CAG to an Arg codon CIG rendering the heteromeric receptor impermeable to Ca 2+ ions. Another example is the editing of 5-HT2C subtype serotonin receptor mRNA resulting in receptor isoforms with reduced G-protein coupling efficiency (reviewed by Gerber and Keller, 2001).<BR>In mice, the editosomes with ADAR proteins require some cis-acting elements like an intronic 'editing-site complementary sequence (ECS)'. Although evolutionarily conserved, the actual role of ECS is not yet elucidated in humans. The editing complex can be generally represented as:<BR>

在人类中，腺苷脱氨化为肌苷的转化是最常见的编辑事件。该过程在脑组织中尤为显著，其所引起的氨基酸变化能够影响多种离子通道的传导。肌苷被翻译机制识别为鸟苷，如同其本身。ADARs（作用于RNA的腺苷脱氨酶）通过作为单个肽段来修饰前体mRNA，并识别RNA中的结构决定因素。截至目前，已知该脱氨酶家族包含三个成员：ADAR 1、ADAR 2和ADAR 3，它们共享一个共同的模块化结构域。ADAR 1和2含有催化脱氨酶结构域、双链RNA结合结构域，并表现出RNA编辑活性。ADAR1活性存在于多种哺乳动物组织中，其中大脑中的浓度最高。越来越多的哺乳动物基因被发现可以通过ADARs发生脱氨化。例如，编码离子型谷氨酸受体（GluRs）亚基的前体mRNA中的编辑导致的脱氨化过程已被广泛研究。在GluR2（GluRB）亚基的Q/R位点的编辑事件将谷氨酰胺密码子CAG转化为精氨酸密码子CIG，使得异聚受体对钙离子不可渗透。另一个例子是5-HT2C型血清素受体mRNA的编辑，导致受体异构体具有降低的G蛋白偶联效率（参见Gerber和Keller，2001年的综述）。在老鼠中，带有ADAR蛋白的编辑复合体需要一些顺式作用元件，如内含子的'编辑位点互补序列（ECS）'。尽管ECS在进化上保守，但其在人类中的实际作用尚未阐明。编辑复合体可以一般性地表示为：