AUTHOR=Mladenova Dessislava , Barry Guy , Konen Lyndsey M. , Pineda Sandy S. , Guennewig Boris , Avesson Lotta , Zinn Raphael , Schonrock Nicole , Bitar Maina , Jonkhout Nicky , Crumlish Lauren , Kaczorowski Dominik C. , Gong Andrew , Pinese Mark , Franco Gloria R. , Walkley Carl R. , Vissel Bryce , Mattick John S. TITLE=Adar3 Is Involved in Learning and Memory in Mice JOURNAL=Frontiers in Neuroscience VOLUME=12 YEAR=2018 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.00243 DOI=10.3389/fnins.2018.00243 ISSN=1662-453X ABSTRACT=

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 KCl-mediated activation in SH-SY5Y cells. These results indicate that ADAR3 contributes to cognitive processes in mammals.