Double-Stranded RNA Adenosine Deaminase And Its Regulatory Role In Gene Expression. E. Ma , L. Chen. Dept Molecular & Cell Biol, Univ California, Berkeley, CA.

   Pre-mRNA editing conducted by double-stranded RNA adenosine deaminase (ADAR) plays an important role in many biological/ physiological processes. ADAR can modulate the neuronal functions by directly editing either coding region of an ion channel mRNA to generate functionally different isoforms or non-coding regions of mRNAs to affect RNA splicing and stability. Drosophila has a single ADAR gene (dADAR) that is expressed exclusively in nervous system. The dADAR null mutant flies display a range of defects, including locomotor deficits, slow recovery from an induced anoxia and age-dependent neurodegeneration. To determine the molecular basis for these effects and to explore biological functions of ADAR in general, we performed cDNA microarray analysis to systematically study the regulatory role of the dADAR protein on global gene expression. Our study revealed that the elimination of dADAR activity in the fly resulted in alteration of many genes. The genes encoding calcium binding proteins and the synaptic proteins are significantly down-regulated while the genes encoding proteases are up-regulated in the mutant flies. The majority of the genes encoding the proteins involved in RNA processing, and protein kinases are up-regulated. Mutation of dADAR also differentially regulated the expression of the genes encoding the proteins involved in defense systems against free-radicals and other stresses. This is a first study demonstrating that dADAR functions not only in pre-mRNA editing to maintain normal neuronal functions but also in the regulation of the expression of many genes involved in diverse functions. Together with detailed characterization of behaviors displayed by the dADAR mutant flies, these data provide the basis for comprehensive understanding of the biological roles of ADAR-regulated pre-mRNA editing.