DataSheet1_Adar3 Is Involved in Learning and Memory in Mice.DOCX (1.05 MB)

DataSheet1_Adar3 Is Involved in Learning and Memory in Mice.DOCX

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posted on 13.04.2018, 12:26 by 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

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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