Dysregulation of RNA editing patterns has been linked with neurological disorders and some cancers. The most studied of these editing events occurs with adenosine deaminases acting on RNA (ADAR), which is a family of three RNA editing proteins, ADAR, ADARB1, and ADARB2. ADARs catalyze the hydraulic deamination of adenosine (A) in pre-mRNA to inosine (I), which is then read as a guanine (G). At least one family member of ADAR is found in nearly every species within Metazoa genomes. However, not much is currently known about the regulation of ADAR expression in these animals. There is evidence of activation by interferon stimulated response elements (ISRE) for ADAR1 expression linking it with the type 1 interferon antiviral response of the innate immune system. Using known ADAR DNA sequences, we investigate the evolutionary patterns observed within the promoter region for ADAR1, ADARB1, and ADARB2 to get insights into the complex regulation of RNA editing seen in the transcriptome. Genomic sequence alignments will be used to reconstruct phylogenetic trees to trace the evolutionary origin of the link between innate immunity and ADAR expression. We are using phylogenetic approaches and HMM signals to identify conserved putative regulatory elements within the promoter region as a way to find common promoter sequences for ADARB1 and ADARB2.
Dr. Olena Piontkivska
Adenosine deaminases acting on RNA (ADAR) are known to be present in almost every metazoan genome. This family of 3 proteins, ADAR1, ADARB1, ADARB2 is responsible for deamination of adenosine (A) in RNA to inosine (I), which is then interpreted as a guanine (G). There is little known about the regulation of expression of ADAR. A type 1 interferon antiviral response elements (ISRE) has been found in ADAR1’s promotor region confirming its link with the innate immune response. However, little is known about the evolution of this regulatory mechanism. Thus, we plan to address this gap in our understanding of the regulation of ADARB1 and ADARB2. Genomic ADAR sequences from multiple completely annotated metazoan genomes will be collected, focusing on the promoter regions. We will use hmm signals to discovers conserved regions within the promoter sequences as well as phylogenic analysis to delineate evolutionary patterns of these promoters in ADAR loci.