Spatiotemporal Regulation of Multiple Overlapping Sense and Novel Natural Antisense Transcripts at the Nrgn and Camk2n1 Gene Loci during Mouse Cerebral Corticogenesis (original) (raw)

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1Department of Molecular Pathology, The Institute of Medical and Veterinary Science and The Hanson Institute, Adelaide, SA 5000, Australia

2School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA 5005, Australia

3Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor DE, Malaysia

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4Pathology Department, The Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia

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5Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia

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5Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia

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6School of Molecular and Biomedical Science, Faculty of Sciences, University of Adelaide, Adelaide, SA 5005, Australia

7Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor DE, Malaysia

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5Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia

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8Howard Florey Institute, The University of Melbourne, Parkville, Victoria 3010, Australia

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1Department of Molecular Pathology, The Institute of Medical and Veterinary Science and The Hanson Institute, Adelaide, SA 5000, Australia

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9Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia

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6School of Molecular and Biomedical Science, Faculty of Sciences, University of Adelaide, Adelaide, SA 5005, Australia

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Published:

06 August 2010

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King-Hwa Ling, Chelsee A. Hewitt, Tim Beissbarth, Lavinia Hyde, Pike-See Cheah, Gordon K. Smyth, Seong-Seng Tan, Christopher N. Hahn, Tim Thomas, Paul Q. Thomas, Hamish S. Scott, Spatiotemporal Regulation of Multiple Overlapping Sense and Novel Natural Antisense Transcripts at the Nrgn and Camk2n1 Gene Loci during Mouse Cerebral Corticogenesis, Cerebral Cortex, Volume 21, Issue 3, 2011, Pages 683–697, https://doi.org/10.1093/cercor/bhq141
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Abstract

Nrgn and Camk2n1 are highly expressed in the brain and play an important role in synaptic long-term potentiation via regulation of Ca2+/calmodulin-dependent protein kinase II. We have shown that the gene loci for these 2 proteins are actively transcribed in the adult cerebral cortex and feature multiple overlapping transcripts in both the sense and antisense orientations with alternative polyadenylation. These transcripts were upregulated in the adult compared with embryonic and P1.5 mouse cerebral cortices, and transcripts with different 3′ untranslated region lengths showed differing expression profiles. In situ hybridization (ISH) analysis revealed spatiotemporal regulation of the Nrgn and Camk2n1 sense and natural antisense transcripts (NATs) throughout cerebral corticogenesis. In addition, we also demonstrated that the expression of these transcripts was organ-specific. Both Nrgn and Camk2n1 sense and NATs were also upregulated in differentiating P19 teratocarcinoma cells. RNA fluorescent ISH analysis confirmed the capability of these NATs to form double-stranded RNA aggregates with the sense transcripts in the cytoplasm of cells obtained from the brain. We propose that the differential regulation of multiple sense and novel overlapping NATs at the Nrgn and Camk2n1 loci will increase the diversity of posttranscriptional regulation, resulting in cell- and time-specific regulation of their gene products during cerebral corticogenesis and function.

© The Author 2010. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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