Determination of editors at the novel A-to-I editing positions.
A-to-I RNA editing modifies a variety of biologically important mRNAs, and is specifically catalyzed by either adenosine deaminase acting on RNA type 1 (ADAR1) or type 2 (ADAR2) in mammals including human. Recently several novel A-to-I editing sites were identified in mRNAs abundantly expressed in mammalian organs by means of computational genomic analysis, but which enzyme catalyzes these editing sites has not been determined. Using RNA interference (RNAi) knockdowns, we found that cytoplasmic fragile X mental retardation protein interacting protein 2 (CYFIP2) mRNA had an ADAR2-mediated editing position and bladder cancer associated protein (BLCAP) mRNA had an ADAR1-mediated editing position. In addition, we found that ADAR2 forms a complex with mRNAs with ADAR2-mediated editing positions including GluR2, kv1.1 and CYFIP2 mRNAs, particularly when the editing sites were edited in human cerebellum by means of immunoprecipitation (IP) method. CYFIP2 mRNA was ubiquitously expressed in human tissues with variable extents of K/E site editing. Because ADAR2 underactivity may be a causative molecular change of death of motor neurons in sporadic amyotrophic lateral sclerosis (ALS), this newly identified ADAR2-mediated editing position may become a useful tool for ALS research.
Nishimoto
Yoshinori
Y
Department of Neurology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Yamashita
Takenari
T
Hideyama
Takuto
T
Tsuji
Shoji
S
Suzuki
Norihiro
N
Kwak
Shin
S
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000243:Adenosine Deaminase / Q000378:metabolism*; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D002531:Cerebellum; D003285:Contractile Proteins / Q000235:genetics; D064448:Filamins; D006801:Humans; D047468:Immunoprecipitation; D008840:Microfilament Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D017393:RNA Editing / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C518673:CYFIP2 protein, human; D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; C104722:glutamate receptor ionotropic, AMPA 2