1. Adar3 is involved in learning and memory in mice
- Author
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Mladenova, D, Barry, G, Konen, LM, Pineda, SS, Guennewig, B, Avesson, L, Zinn, R, Schonrock, N, Bitar, M, Jonkhout, N, Crumlish, L, Kaczorowski, DC, Gong, A, Pinese, M, Franco, GR, Walkley, CR, Vissel, B, Mattick, JS, Mladenova, D, Barry, G, Konen, LM, Pineda, SS, Guennewig, B, Avesson, L, Zinn, R, Schonrock, N, Bitar, M, Jonkhout, N, Crumlish, L, Kaczorowski, DC, Gong, A, Pinese, M, Franco, GR, Walkley, CR, Vissel, B, and Mattick, JS
- 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.
- Published
- 2018