Lai F, Chen C X, Lee V M, Nishikura K
Wistar Institute, Philadelphia, Pennsylvania 19104, U.S.A.
J Neurochem. 1997 Jul;69(1):43-52. doi: 10.1046/j.1471-4159.1997.69010043.x.
RNA editing plays an important role in determining physiological characteristics of certain glutamate-gated receptor (GluR) channels such as Ca2+ permeability and desensitization kinetics. In one case, the editing changes a gene-encoded glutamine (Q) to an arginine (R) codon located in the channel-forming domain of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit GluR-B and also the kainate receptor subunits GluR5 and GluR6. Another case of RNA editing alters an arginine (R) to a glycine (G) codon at a position termed the "R/G" site of AMPA subunits GluR-B, C, and D. Double-stranded RNA-specific adenosine deaminases (DRADA) have been implicated as agents involved in the editing. By using a human teratocarcinoma cell line, NT2, we investigated the change of the RNA editing of GluR subunits in conjunction with the expression of two DRADA members, DRADA1 and DRADA2 genes, during neuronal differentiation. Whereas Q/R and R/G site RNA editing both become progressively activated in differentiating NT2 cells, the expression of the two DRADA genes can already be detected even in the undifferentiated NT2 cells. Development of the editing machinery appears to require, in addition to DRADA enzymes, a currently unidentified mechanism(s) that may become activated during neuronal differentiation.
RNA 编辑在决定某些谷氨酸门控受体（GluR）通道的生理特性方面发挥着重要作用，比如钙离子通透性和脱敏动力学。在一个实例中，编辑将一个基因编码的谷氨酰胺（Q）转变为精氨酸（R）密码子，该密码子位于α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体亚基GluR-B以及海人藻酸受体亚基GluR5和GluR6的通道形成结构域中。RNA 编辑的另一个实例是，在AMPA亚基GluR-B、C和D的一个被称为“R/G”位点的位置，将精氨酸（R）密码子改变为甘氨酸（G）密码子。双链RNA特异性腺苷脱氨酶（DRADA）被认为是参与编辑的因子。通过使用人畸胎瘤细胞系NT2，我们研究了在神经元分化过程中，GluR亚基的RNA编辑变化以及两个DRADA成员DRADA1和DRADA2基因的表达情况。虽然在分化的NT2细胞中，Q/R和R/G位点的RNA编辑都逐渐被激活，但即使在未分化的NT2细胞中也已经能够检测到这两个DRADA基因的表达。除了DRADA酶之外，编辑机制的发育似乎还需要一种目前尚未明确的机制，这种机制可能在神经元分化过程中被激活。
