a neighboring intron but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS). Location The editing site was previously believed to be a single nucleotide polymorphism. The editing site is found at amino acid 5 of transmembrane domain 3 of exon 9. The predicted double-stranded RNA structure is interrupted by three bulges and a mismatch at the editing site. The double-stranded region is 22 base pairs in length. As with editing of the KCNA1 gene product, the editing region and the editing complementary sequence are both found in exonic regions. In the pre=mRNA of GABRA3, both are found within exon 9. The other subunits of the receptor are thought not to be edited, as their predicted secondary structure is less likely to be edited. Also, alpha subunits 1 and 6 have a uridine instead of an adenosine at the site corresponding to the editing site in alpha subunit 3. Point mutation experiments determined that a Cytidine 15 nucleotides from the editing site is the base opposite the edited base. Using a GABRA3 mini-gene that encodes for exon 9 cotransfected to HEK293 cells with either ADAR1 or -2 or none, it was determined that both active ADARs can efficiently edited the site in exon 9. Regulation The mRNA expression of the alpha 3 subunit is developmentally regulated. It is the dominant subunit in the forebrain tissue at birth, gradually decreasing in prominence as alpha subunit 1 takes over. Also experiments with mice have demonstrated that editing of pre-mRNA alpha 3 subunit increases from 50% at birth to nearly 100% in adult. Editing levels are lower in the hippocampus Conservation At the location corresponding to the I/M site of GABRA3 in frog and pufferfish there is a genomically encoded methionine. In all other species, there is an isoleucine at the position. Consequences Structure Editing results in a codon change from (AUA) I to (AUG) M at the editing site. This results in translation of a methionine instead of an isoleucine at the I/M site. The amino acid change occurs in the transmembrane domain 3. The 4 transmembrane domains of each of the 5 subunits that make up the receptor interact to form the receptor channel. It is likely that the change of amino acids disturbs the structure, effecting gating and inactivation of the channel. This is because methionine has