Low editing efficiency of GluR2 mRNA is associated with a low relative abundance of ADAR2 mRNA in white matter of normal human brain
Low editing efficiency of GluR2 mRNA is associated with a low relative abundance of ADAR2 mRNA in white matter of normal human brain
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DOI：
10.1046/j.1460-9568.2003.02718.x
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发表时间：
2003-07-01
影响因子：
3.4
通讯作者：
Kwak, S
中科院分区：
文献类型：
--
作者：
Kawahara, Y;Ito, K;Kwak, S
离子型谷氨酸受体（GluR）亚基GluR 2、GluR 5和GluR 6在它们的Q/R位点进行RNA编辑，导致受体的通道特性的显著改变。在GluRs的Q/R位点的RNA编辑是发育和区域调节的。在这里，我们提供了第一个定量测量的GluR亚基和RNA编辑酶ADAR 1-ADAR 3的mRNA在Q/R位点的编辑效率与阿达尔mRNA在人脑中的表达水平的比较。我们证明了在白色物质中GluRs的Q/R位点的编辑显著少于灰质。此外，通过定量逆转录-聚合酶链反应方法，我们证明了ADAR 2 mRNA与GluR 2 mRNA的相对丰度在白色物质中显著低于灰质，并且只有当ADAR 2 mRNA（而不是ADAR 1 mRNA）与GluR 2 mRNA的比值低于阈值（20 x 10（-3））时，GluR 2 Q/R位点编辑才会减少。这些结果表明，GluRs编辑的Q/R位点是以区域性的方式调节的，因此可能是细胞特异性的，并且GluR 2 Q/R位点编辑在人脑中受到ADAR 2的关键调节。
The ionotropic glutamate receptor (GluR) subunits GluR2, GluR5 and GluR6 are subject to RNA editing at their Q/R sites, resulting in significant alterations in the channel properties of the receptors. RNA editing at the Q/R site of GluRs is both developmentally and regionally regulated. Here we provide the first quantitative measurements of both mRNAs of the GluR subunits and mRNAs of the RNA editing enzymes ADAR1-ADAR3 in a comparison of the efficiency of editing at the Q/R site with the expression levels of ADAR mRNA in human brain. We demonstrate that the Q/R site of GluRs in white matter is edited significantly less than in grey matter. In addition, by means of quantitative reverse transcription-polymerase chain reaction methods, we demonstrate that the relative abundance of ADAR2 mRNA to GluR2 mRNA is significantly lower in white matter than in grey matter and that the GluR2 Q/R site editing decreased only when the ratio of ADAR2 mRNA (not that of ADAR1 mRNA) to GluR2 mRNA dropped below a threshold (20 x 10(-3)). These results suggest that Q/R site of GluRs editing is regulated in a regional, and hence presumably cell-specific, manner and that the GluR2 Q/R site editing is critically regulated by ADAR2 in human brain.