Adar3 Is Involved in Learning and Memory in Mice
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 editi...
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Frontiers Media S.A.
2018-04-01
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Series: | Frontiers in Neuroscience |
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Online Access: | http://journal.frontiersin.org/article/10.3389/fnins.2018.00243/full |
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English |
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Article |
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DOAJ |
author |
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 |
spellingShingle |
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 Adar3 Is Involved in Learning and Memory in Mice Frontiers in Neuroscience ADAR3 Adar3exon3 mouse model RNA editing learning and memory Adarb2 |
author_facet |
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 |
author_sort |
Dessislava Mladenova |
title |
Adar3 Is Involved in Learning and Memory in Mice |
title_short |
Adar3 Is Involved in Learning and Memory in Mice |
title_full |
Adar3 Is Involved in Learning and Memory in Mice |
title_fullStr |
Adar3 Is Involved in Learning and Memory in Mice |
title_full_unstemmed |
Adar3 Is Involved in Learning and Memory in Mice |
title_sort |
adar3 is involved in learning and memory in mice |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2018-04-01 |
description |
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. |
topic |
ADAR3 Adar3exon3 mouse model RNA editing learning and memory Adarb2 |
url |
http://journal.frontiersin.org/article/10.3389/fnins.2018.00243/full |
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doaj-035a01122d1e4d05b15faa12ae756e8d2020-11-25T01:56:38ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-04-011210.3389/fnins.2018.00243353124Adar3 Is Involved in Learning and Memory in MiceDessislava Mladenova0Dessislava Mladenova1Guy Barry2Guy Barry3Lyndsey M. Konen4Lyndsey M. Konen5Lyndsey M. Konen6Sandy S. Pineda7Sandy S. Pineda8Boris Guennewig9Boris Guennewig10Lotta Avesson11Raphael Zinn12Raphael Zinn13Raphael Zinn14Nicole Schonrock15Nicole Schonrock16Maina Bitar17Maina Bitar18Nicky Jonkhout19Nicky Jonkhout20Lauren Crumlish21Dominik C. Kaczorowski22Andrew Gong23Mark Pinese24Mark Pinese25Gloria R. Franco26Carl R. Walkley27Bryce Vissel28Bryce Vissel29Bryce Vissel30John S. Mattick31John S. Mattick32Garvan Institute of Medical Research, Sydney, NSW, AustraliaSt. Vincent's Clinical School, University of New South Wales, Sydney, NSW, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaSt. Vincent's Clinical School, University of New South Wales, Sydney, NSW, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaCentre for Neuroscience and Regenerative Medicine, Faculty of Science, University of Technology Sydney, Sydney, NSW, AustraliaSt. Vincent's Centre for Applied Medical Research (AMR), Sydney, NSW, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaSt. Vincent's Clinical School, University of New South Wales, Sydney, NSW, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaSt. Vincent's Clinical School, University of New South Wales, Sydney, NSW, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaCentre for Neuroscience and Regenerative Medicine, Faculty of Science, University of Technology Sydney, Sydney, NSW, AustraliaSt. Vincent's Centre for Applied Medical Research (AMR), Sydney, NSW, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaSt. Vincent's Clinical School, University of New South Wales, Sydney, NSW, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaSt. Vincent's Clinical School, University of New South Wales, Sydney, NSW, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaSt. Vincent's Clinical School, University of New South Wales, Sydney, NSW, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaSt. Vincent's Clinical School, University of New South Wales, Sydney, NSW, AustraliaDepartamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilSt. Vincent's Institute of Medical Research, Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, VIC, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaCentre for Neuroscience and Regenerative Medicine, Faculty of Science, University of Technology Sydney, Sydney, NSW, AustraliaSt. Vincent's Centre for Applied Medical Research (AMR), Sydney, NSW, AustraliaGarvan Institute of Medical Research, Sydney, NSW, AustraliaSt. Vincent's Clinical School, University of New South Wales, Sydney, NSW, AustraliaThe 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.http://journal.frontiersin.org/article/10.3389/fnins.2018.00243/fullADAR3Adar3exon3 mouse modelRNA editinglearning and memoryAdarb2 |