Low editing efficiency of GluR2 mRNA is associated with a low relative abundance of ADAR2 mRNA in white matter of normal human brain.
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.
Kawahara
Yukio
Y
Department of Neurology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Ito
Kyoko
K
Sun
Hui
H
Kanazawa
Ichiro
I
Kwak
Shin
S
D000243:Adenosine Deaminase / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D000368:Aged; D001923:Brain Chemistry / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017393:RNA Editing / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA / Q000096:biosynthesis* / Q000235:genetics; D018092:Kainic Acid Receptors / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D000097806:GluK2 Kainate Receptor
D000243:Adenosine Deaminase; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor; C567955:ADARB1 protein, human; C104722:glutamate receptor ionotropic, AMPA 2