Editing modifies the GABA(A) receptor subunit alpha3

RNA. 2007 May;13(5):698-703. doi: 10.1261/rna.349107. Epub 2007 Mar 16.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / genetics
  • Adenosine Deaminase / metabolism
  • Animals
  • Animals, Newborn
  • Brain / growth & development
  • Cells, Cultured
  • Gene Expression Regulation, Developmental
  • Humans
  • Isoleucine / metabolism
  • Methionine / metabolism
  • Mice
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • RNA Editing
  • RNA-Binding Proteins
  • Receptors, GABA-A / genetics*
  • Receptors, GABA-A / metabolism*

Substances

  • GABRA3 protein, human
  • Gabra3 protein, mouse
  • RNA-Binding Proteins
  • Receptors, GABA-A
  • Isoleucine
  • Methionine
  • ADARB1 protein, human
  • Adenosine Deaminase