Adar3 Is Involved in Learning and Memory in Mice
The amount of regulatory RNA encoded in the genome and the extent of RNA editing by the post-transcriptional deamination of adenosine to inosine (A-I) have increased with developmental complexity and may be an important factor in the cognitive evolution of animals. The newest member of the A-I editing family of ADAR proteins, the vertebrate-specific ADAR3, is highly expressed in the brain, but its functional significance is unknown. In vitro studies have suggested that ADAR3 acts as a negative regulator of A-I RNA editing but the scope and underlying mechanisms are also unknown. Meta-analysis of published data indicates that mouse Adar3 expression is highest in the hippocampus, thalamus, amygdala, and olfactory region. Consistent with this, we show that mice lacking exon 3 of Adar3 (which encodes two double stranded RNA binding domains) have increased levels of anxiety and deficits in hippocampus-dependent short- and long-term memory formation. RNA sequencing revealed a dysregulation of genes involved in synaptic function in the hippocampi of Adar3-deficient mice. We also show that ADAR3 transiently translocates from the cytoplasm to the nucleus upon KCI-mediated activation in SH-SY5Y cells. These results indicate that ADAR3 contributes to cognitive processes in mammals.
|Authors||Mladenova, D.; Barry, G.; Konen, L. M.; Pineda, S. S.; Guennewig, B.; Avesson, L.; Zinn, R.; Schonrock, N.; Bitar, M.; Jonkhout, N.; Crumlish, L.; Kaczorowski, D. C.; Gong, A.; Pinese, M.; Franco, G. R.; Walkley, C. R.; Vissel, B.; Mattick, J. S.|
|Responsible Garvan Author|
|Publisher Name||Frontiers in Neuroscience|
|URL link to publisher's version||<Go to ISI>://WOS:000429977800001|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/14524|