© 2007 Oxford University Press
The Chemistry and Biology of RNA editing by Adenosine Deaminases
Department of Chemistry, University of California, Davis, CA 95616, USA
*Corresponding author. E-mail: beal{at}chem.ucdavis.edu
Abstract
Deamination of adenosines within mRNAs catalyzed by ADAR enzymes generates inosines at the corresponding nucleotide positions. Since inosine is decoded as guanosine, this reaction can lead to codon changes and the introduction of amino acids into a gene product not encoded in the gene. Translation of the different coding strands created by this process leads to protein structural diversity in the parent organism and is necessary for nervous system function in metazoa. The basis for selective editing of adenosines within certain codons is not well understood at the structural/biochemical level. Here we describe the use of synthetic nucleoside analogs incorporated into RNA editing substrates via the protected phosphoramidites to define aspects of the editing reaction mechanism and to carry out mechanism-based trapping of ADAR-RNA complexes. In addition, a high-throughput screen has been developed capable of rapidly identifying functional editing systems.