Adar3 is involved in learning and memory in mice

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

Adar3 is involved in learning and memory in mice

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

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Publication Type:: Journal Article
Citation:: Frontiers in Neuroscience, 2018, 12 (APR)
Issue Date:: 2018-04-13

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Field	Value	Language
dc.contributor.author	Mladenova, D	en_US
dc.contributor.author	Barry, G	en_US
dc.contributor.author	Konen, LM	en_US
dc.contributor.author	Pineda, SS	en_US
dc.contributor.author	Guennewig, B	en_US
dc.contributor.author	Avesson, L	en_US
dc.contributor.author	Zinn, R https://orcid.org/0000-0003-4278-5881	en_US
dc.contributor.author	Schonrock, N	en_US
dc.contributor.author	Bitar, M	en_US
dc.contributor.author	Jonkhout, N	en_US
dc.contributor.author	Crumlish, L	en_US
dc.contributor.author	Kaczorowski, DC	en_US
dc.contributor.author	Gong, A	en_US
dc.contributor.author	Pinese, M	en_US
dc.contributor.author	Franco, GR	en_US
dc.contributor.author	Walkley, CR	en_US
dc.contributor.author	Vissel, B https://orcid.org/0000-0001-8860-8050	en_US
dc.contributor.author	Mattick, JS	en_US
dc.date.available	2018-03-27	en_US
dc.date.issued	2018-04-13	en_US
dc.identifier.citation	Frontiers in Neuroscience, 2018, 12 (APR)	en_US
dc.identifier.issn	1662-4548	en_US
dc.identifier.uri	http://hdl.handle.net/10453/126090
dc.description.abstract	© 2018 Mladenova, Barry, Konen, Pineda, Guennewig, Avesson, Zinn, Schonrock, Bitar, Jonkhout, Crumlish, Kaczorowski, Gong, Pinese, Franco, Walkley, Vissel and Mattick. 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.	en_US
dc.relation.ispartof	Frontiers in Neuroscience	en_US
dc.relation.isbasedon	10.3389/fnins.2018.00243	en_US
dc.title	Adar3 is involved in learning and memory in mice	en_US
dc.type	Journal Article
utslib.citation.volume	APR	en_US
utslib.citation.volume	12	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	1702 Cognitive Sciences	en_US
utslib.for	1701 Psychology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	APR	en_US
pubs.publication-status	Published	en_US
pubs.volume	12	en_US

Abstract:

© 2018 Mladenova, Barry, Konen, Pineda, Guennewig, Avesson, Zinn, Schonrock, Bitar, Jonkhout, Crumlish, Kaczorowski, Gong, Pinese, Franco, Walkley, Vissel and Mattick. 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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http://hdl.handle.net/10453/126090