Frontiers in Neuroscience (Apr 2018)
Adar3 Is Involved in Learning and Memory in Mice
- Dessislava Mladenova,
- Dessislava Mladenova,
- Guy Barry,
- Guy Barry,
- Lyndsey M. Konen,
- Lyndsey M. Konen,
- Lyndsey M. Konen,
- Sandy S. Pineda,
- Sandy S. Pineda,
- Boris Guennewig,
- Boris Guennewig,
- Lotta Avesson,
- Raphael Zinn,
- Raphael Zinn,
- Raphael Zinn,
- Nicole Schonrock,
- Nicole Schonrock,
- Maina Bitar,
- Maina Bitar,
- Nicky Jonkhout,
- Nicky Jonkhout,
- Lauren Crumlish,
- Dominik C. Kaczorowski,
- Andrew Gong,
- Mark Pinese,
- Mark Pinese,
- Gloria R. Franco,
- Carl R. Walkley,
- Bryce Vissel,
- Bryce Vissel,
- Bryce Vissel,
- John S. Mattick,
- John S. Mattick
Affiliations
- Dessislava Mladenova
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Dessislava Mladenova
- St. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Guy Barry
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Guy Barry
- St. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Lyndsey M. Konen
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Lyndsey M. Konen
- Centre for Neuroscience and Regenerative Medicine, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia
- Lyndsey M. Konen
- St. Vincent's Centre for Applied Medical Research (AMR), Sydney, NSW, Australia
- Sandy S. Pineda
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Sandy S. Pineda
- St. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Boris Guennewig
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Boris Guennewig
- St. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Lotta Avesson
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Raphael Zinn
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Raphael Zinn
- Centre for Neuroscience and Regenerative Medicine, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia
- Raphael Zinn
- St. Vincent's Centre for Applied Medical Research (AMR), Sydney, NSW, Australia
- Nicole Schonrock
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Nicole Schonrock
- St. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Maina Bitar
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Maina Bitar
- St. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Nicky Jonkhout
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Nicky Jonkhout
- St. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Lauren Crumlish
- Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, Australia
- Dominik C. Kaczorowski
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Andrew Gong
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Mark Pinese
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Mark Pinese
- St. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Gloria R. Franco
- Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Carl R. Walkley
- St. Vincent's Institute of Medical Research, Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, VIC, Australia
- Bryce Vissel
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- Bryce Vissel
- Centre for Neuroscience and Regenerative Medicine, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia
- Bryce Vissel
- St. Vincent's Centre for Applied Medical Research (AMR), Sydney, NSW, Australia
- John S. Mattick
- Garvan Institute of Medical Research, Sydney, NSW, Australia
- John S. Mattick
- St. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- DOI
- https://doi.org/10.3389/fnins.2018.00243
- Journal volume & issue
-
Vol. 12
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.
Keywords
