Editing modifies the GABA(A) receptor subunit alpha3.
Adenosine to inosine (A-to-I) pre-mRNA editing by the ADAR enzyme family has the potential to increase the variety of the proteome. This editing by adenosine deamination is essential in mammals for a functional brain. To detect novel substrates for A-to-I editing we have used an experimental method to find selectively edited sites and combined it with bioinformatic techniques that find stem-loop structures suitable for editing. We present here the first verified editing candidate detected by this screening procedure. We show that Gabra-3, which codes for the alpha3 subunit of the GABA(A) receptor, is a substrate for editing by both ADAR1 and ADAR2. Editing of the Gabra-3 mRNA recodes an isoleucine to a methionine. The extent of editing is low at birth but increases with age, reaching close to 100% in the adult brain. We therefore propose that editing of the Gabra-3 mRNA is important for normal brain development.
Ohlson
Johan
J
Department of Molecular Biology and Functional Genomics, Stockholm University, SE-106 91 Stockholm, Sweden.
Pedersen
Jakob Skou
JS
Haussler
David
D
Ohman
Marie
M
D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007532:Isoleucine / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D017393:RNA Editing; D016601:RNA-Binding Proteins; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism*
C546257:GABRA3 protein, human; C546258:Gabra3 protein, mouse; D016601:RNA-Binding Proteins; D011963:Receptors, GABA-A; D007532:Isoleucine; D008715:Methionine; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase