Brown BIOL1220:Notebook/SynBio in Theory and Practice/Genes/ADAR

The Functions of the ADAR Family

 * Three members of this deaminase family are known: ADAR 1, ADAR 2, and ADAR 3 that share a common modular domain structure.
 * ADARs modify pre-mRNA and recognize structural determinants in the RNA.
 * In mice, the editosomes with ADAR proteins require some cis-acting elements like an intronic 'editing-site complementary sequence (ECS)'. Although evolutionarily conserved, the actual role of ECS is not yet elucidated in humans. A representation of the editing complex is shown below.
 * The deamination of adenosines (A) to inosine (I) is the most common editing event.

Why edit pre-mRNA?

 * To increase genetic diversity through changes in the transcriptome. For an example of this, see below.

ADAR Functions in Receptors

 * Deamination by editing in pre-mRNAs encodes a variety of subunits of ionotropic glutamate receptors (GluRs).
 * Editing at the Q/R site of the GluR2 (GluRB) subunit of AMPA receptors changes a Gln codon CAG to an Arg codon CIG, which makes the heteromeric receptor impermeable to Ca2+ ions.
 * Editing of 5-HT2C subtype serotonin receptor mRNA results in receptor isoforms with reduced G-protein coupling efficiency (reviewed by Gerber and Keller, 2001).