Evidence from comparative genome analyses suggests that organismal complexity and diversity by and large arise from increasingly more elaborate regulation of gene expression rather than through the invention of novel genes. An important mechanism for the generation of molecular diversity in mammals is pre-mRNA editing by A-to-I modification. It increases RNA and protein diversity and regulates key functional properties of neurotransmitter receptors in the central nervous system by changing single codons in pre-mRNA. The editing machinery specifically targets single nucleotides for editing within partially double-stranded pre-mRNA structures. The deficiency or misregulation of editing has been implicated in the etiology of neurological diseases, such as epilepsy, amyotrophic lateral sclerosis (ALS), depression and tumor progression.

We have recently identified Alu repeat elements in the human genome as a major target for post-transcriptional processing by A-to-I RNA editing. These findings suggest additional roles for RNA editing and links it to other RNA processing phenomena, such as alternative pre-mRNA splicing as well as siRNA mediated gene silencing and miRNA function. We and others have further mapped RNA editing events to micro RNA precursor sequences that suggest changes for the processing of miRNAs and miRNA target specificity. The long term goals of our ongoing studies are to determine the prevalence of A-to-I RNA editing in the human transcriptome, to characterize the functional consequences of editing for the targeted genes and to obtain insights into regulatory mechanisms for RNA editing in vivo.