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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Main Authors: Dessislava Mladenova, Guy Barry, Lyndsey M. Konen, Sandy S. Pineda, Boris Guennewig, Lotta Avesson, Raphael Zinn, Nicole Schonrock, Maina Bitar, Nicky Jonkhout, Lauren Crumlish, Dominik C. Kaczorowski, Andrew Gong, Mark Pinese, Gloria R. Franco, Carl R. Walkley, Bryce Vissel, John S. Mattick
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-04-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fnins.2018.00243/full
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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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spelling 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