Ohlson Johan, Pedersen Jakob Skou, Haussler David, Ohman Marie
Department of Molecular Biology and Functional Genomics, Stockholm University, SE-106 91 Stockholm, Sweden.
RNA. 2007 May;13(5):698-703. doi: 10.1261/rna.349107. Epub 2007 Mar 16.
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.
ADAR 酶家族介导的腺苷到肌苷(A 到 I)的前体 mRNA 编辑有潜力增加蛋白质组的多样性。这种通过腺苷脱氨基作用进行的编辑对于哺乳动物功能性大脑至关重要。为了检测 A 到 I 编辑的新底物,我们使用了一种实验方法来选择性地找到编辑位点,并将其与生物信息学技术相结合,以找到适合编辑的茎环结构。我们在此展示了通过该筛选程序检测到的首个经证实的编辑候选物。我们发现,编码 GABA(A)受体α3 亚基的 Gabra-3 是 ADAR1 和 ADAR2 的编辑底物。Gabra-3 mRNA 的编辑将异亮氨酸重新编码为甲硫氨酸。编辑程度在出生时较低,但随年龄增长而增加,在成人大脑中接近 100%。因此,我们认为 Gabra-3 mRNA 的编辑对正常大脑发育很重要。