Adar3 Is Involved in Learning and Memory in Mice

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Mladenova, D; Barry, G; Konen, LM; Pineda, SS; Guennewig, B; Avesson, L; Zinn, R; Schonrock, N; Bitar, M; Jonkhout, N; ...Date
2018-04-13Source Title
Frontiers in NeurosciencePublisher
FRONTIERS MEDIA SAUniversity of Melbourne Author/s
Walkley, CarlAffiliation
Medicine and RadiologyMetadata
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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. (2018). Adar3 Is Involved in Learning and Memory in Mice. FRONTIERS IN NEUROSCIENCE, 12 (APR), https://doi.org/10.3389/fnins.2018.00243.Access Status
Open AccessAbstract
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.
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