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    Adar3 Is Involved in Learning and Memory in Mice

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    Author
    Mladenova, D; Barry, G; Konen, LM; Pineda, SS; Guennewig, B; Avesson, L; Zinn, R; Schonrock, N; Bitar, M; Jonkhout, N; ...
    Date
    2018-04-13
    Source Title
    Frontiers in Neuroscience
    Publisher
    FRONTIERS MEDIA SA
    University of Melbourne Author/s
    Walkley, Carl
    Affiliation
    Medicine and Radiology
    Metadata
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    Document Type
    Journal Article
    Citations
    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 Access
    URI
    http://hdl.handle.net/11343/254995
    DOI
    10.3389/fnins.2018.00243
    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.

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