That of the squid Loligo pealeii contains an ADAR2-like gene (sq ADAR2) that produces variants (a and b) through alternative splicing. The human genome contains three ADAR genes (h ADAR1 to 3). The deaminase domain is depicted in purple, while the dsRBMs are shown in orange and Z-DNA binding domains, unique to human ADAR1, are presented in green. (a) Domain architecture of metazoan ADARs. In contrast, ADAR genes do not appear to be present in fungal, plant and yeast genomes. Furthermore, ADAR genes are also present in the genomes of both sea urchin and sea anemone, suggesting an early origin of RNA editing enzymes in metazoan evolution. In addition, the squid and hydra (RA Reenan, unpublished results) genomes each encode a single adar locus, while the chicken and zebrafish genomes encode two and four adar genes, respectively. The Caenorhabditis elegans genome encodes two genes, Ce ADR1 and Ce ADR2, while only a single adar locus is present in the Drosophila genome (Figure 1a).
Mammalian genomes encode three ADARs: ADAR1 and ADAR2, which are catalytically active, and ADAR3, which is thought to be catalytically inactive. These enzymes, discovered over 25 years ago, are highly conserved in metazoa, although the number of genes and isoforms varies between species. Adenosine-to-inosine (A-to-I) RNA 'editing,' therefore, effectively changes the primary sequence of RNA targets. Because the properties of inosine mimic those of guanosine (inosine will form two hydrogen bonds with cytosine, for example), inosine is recognized as guanosine by the translational cellular machinery. Here, we present a review on the current knowledge regarding the ADAR protein family, including evolutionary history, key structural features, localization, function and mechanism.Īdenosine deaminases acting on RNA (ADARs) are enzymes that catalyze the chemical conversion of adenosines to inosines in double-stranded RNA (dsRNA) substrates. Not only does the process of RNA editing alter important nervous system peptides, but ADARs also regulate gene expression through modification of dsRNA substrates that enter the RNA interference (RNAi) pathway and may then act at the chromatin level. Mutation or deletion of ADAR genes results in striking phenotypes, including seizure episodes, extreme uncoordination, and neurodegeneration. Most RNA editing sites in these nervous system targets result in non-synonymous codon changes in functionally important, usually conserved, residues and RNA editing deficiencies in various model organisms bear out a crucial role for ADARs in nervous system function. Once in the nucleus, ADARs participate in the modification of specific adenosines in pre-mRNAs of proteins involved in electrical and chemical neurotransmission, including pre-synaptic release machineries, and voltage- and ligand-gated ion channels. ADAR family members are highly expressed in the metazoan nervous system, where these enzymes predominantly localize to the neuronal nucleus. All ADARs share a common domain architecture consisting of a variable number of amino-terminal dsRNA binding domains (dsRBDs) and a carboxy-terminal catalytic deaminase domain. A highly conserved group of enzymes, the adenosine deaminase acting on RNA (ADAR) family, mediates this reaction. Furthermore, collaboration with colleagues will be easier than ever because MacVector lets you customize graphic results and export them for high-quality printing.Adenosine to inosine (A-to-I) RNA editing is a post-transcriptional process by which adenosines are selectively converted to inosines in double-stranded RNA (dsRNA) substrates. You'll be amazed at how quickly you can flow from task to task with just a few mouse clicks. With MacVector, you can view the results of any analysis in graphical or text format.Īll analysis, editing, and display functions are contained within a single application, so not only will you find MacVector remarkably user-friendly, but you'll also save time, whether you're exploring gene relationships, predicting coding sequences, or conducting cloning experiments. MacVector is a complex tool that provides sequence editing, primer design, Internet database searches, protein analysis, sequence confirmation, contig assembly capabilities, multiple sequence alignment, phylogenetic reconstruction, coding region analysis, Researchers who want a simple, but comprehensive, desktop sequence analysis application continually turn to MacVector, the leading sequence analysis package for the Macintosh.
It features an intuitive interface that integrates a wide variety of industry standard analysis and data mining algorithms into a single application. MacVector is a general DNA and Protein sequence analysis, manipulation and documentation program.