Conditional Knockout of Tumor Overexpressed Gene in Mouse Neurons Affects RNA Granule Assembly,Granule Translation,LTP and Short Term Habituation |
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| Authors: | Elisa Barbarese Marius F. Ifrim Lawrence Hsieh Caiying Guo Vedakumar Tatavarty Michael J. Maggipinto George Korza Jessica W. Tutolo Anthony Giampetruzzi Hien Le Xin-Ming Ma Eric Levine Brian Bishop Duck O. Kim Shigeyuki Kuwada John H. Carson |
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| Affiliation: | 1. Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut, United States of America.; 2. Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, Farmington, Connecticut, United States of America.; 3. Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut, United States of America.; Western University of Health Sciences, United States of America, |
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| Abstract: | In neurons, specific RNAs are assembled into granules, which are translated in dendrites, however the functional consequences of granule assembly are not known. Tumor overexpressed gene (TOG) is a granule-associated protein containing multiple binding sites for heterogeneous nuclear ribonucleoprotein (hnRNP) A2, another granule component that recognizes cis-acting sequences called hnRNP A2 response elements (A2REs) present in several granule RNAs. Translation in granules is sporadic, which is believed to reflect monosomal translation, with occasional bursts, which are believed to reflect polysomal translation. In this study, TOG expression was conditionally knocked out (TOG cKO) in mouse hippocampal neurons using cre/lox technology. In TOG cKO cultured neurons granule assembly and bursty translation of activity-regulated cytoskeletal associated (ARC) mRNA, an A2RE RNA, are disrupted. In TOG cKO brain slices synaptic sensitivity and long term potentiation (LTP) are reduced. TOG cKO mice exhibit hyperactivity, perseveration and impaired short term habituation. These results suggest that in hippocampal neurons TOG is required for granule assembly, granule translation and synaptic plasticity, and affects behavior. |
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