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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. A highly food styling classes conserved group of enzymes, the adenosine deaminase acting on RNA (ADAR) family, mediates this reaction. food styling classes 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. ADAR family members food styling classes are highly expressed in the metazoan nervous system, where these enzymes predominantly localize to the neuronal nucleus. 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. 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. Mutation or deletion of ADAR genes results in striking phenotypes, including seizure episodes, extreme uncoordination, and neurodegeneration. Not only does the process food styling classes of RNA editing alter important nervous system peptides, but ADARs also regulate gene expression through modification food styling classes of dsRNA substrates food styling classes that enter the RNA interference (RNAi) pathway and may then act at the chromatin level. Here, we present a review on the current knowledge regarding the ADAR protein family, including evolutionary history, key structural food styling classes features, localization, function and mechanism. Keywords: ADAR; chromatin; deaminase; dsRNA binding food styling classes proteins; inosine; miRNA; post-transcriptional modification; RNA editing; RNAi; RNA splicing; siRNA Gene organization food styling classes and evolutionary history
Adenosine deaminases acting on RNA (ADARs) are enzymes that catalyze the chemical conversion of adenosines to inosines in double-stranded RNA (dsRNA) substrates. 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 [ 1 ]. Adenosine-to-inosine (A-to-I) RNA 'editing,' therefore, effectively changes the primary sequence of RNA targets.
These enzymes, discovered over 25 years ago [ 2 ], are highly conserved in metazoa [ 3 ], although the number of genes and isoforms varies between species. Mammalian genomes encode three ADARs: ADAR1 and ADAR2, food styling classes which are catalytically food styling classes active [ 4 ], and ADAR3, which is thought to be catalytically inactive [ 5 ]. The Caenorhabditis elegans genome encodes food styling classes two genes, Ce ADR1 and Ce ADR2 [ 6 ], while only a single adar locus is present in the Drosophila genome [ 7 ] (Figure 1a ). In addition, the squid [ 8 ] and hydra (RA Reenan, unpublished results) genomes each encode a single adar locus, while the chicken and zebrafish genomes food styling classes encode two and four adar genes, respectively [ 9 ]. Furthermore, ADAR genes are also present in the genomes of both sea urchin and sea anemone, suggesting an early origin of RNA editing food styling classes enzymes in metazoan evolution [ 9 ]. In contrast, ADAR genes do not appear to be present in fungal, plant and yeast genomes [ 9 ].
Figure 1. The ADAR family protein . (a) Domain architecture of metazoan ADARs. The deaminase domain is depicted in purple, while the dsRBMs are shown in orange and Z-DNA binding food styling classes domains, unique to human ADAR1 , are presented in green. food styling classes The human genome contains three ADAR genes (h ADAR1 to 3 ). That of the squid Loligo pealeii contains an ADAR2-like gene (sq ADAR2 ) that produces variants (a and b) through alternative splicing. C. elegans contains two genes (ce ADAR1 and 2 ), while the genome food styling classes of D. melanogaster encodes only one (dADAR), an enzyme homologous to hADAR2. Although the dsRBMs found in the Hydra magnapapillata genome are highly divergent, five such motifs are recognizable in hm ADAR , the only identified gene in this species. Human and Drosophila food styling classes ADAT architectures are included (red), as these enzymes are believed to be ancestral to present-day ADARs. (b) Cladogram based on ADAR catalytic domain sequences. MacVector was used to generate a relatedness tree based on the protein sequences of ADAR catalytic domains from different species. C. elegans ADAR2 is absent due to difficulty aligning the catalytic domain. Note that human and Drosophila ADATs (red) cluster as the outgroup.