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Mol Psychiatry. 2014 Apr;19(4):486-94. doi: 10.1038/mp.2013.45. Epub 2013 Apr 30.

The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing.

Author information

1
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
2
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.
3
Department of Neuroscience, Neurology and Ophthalmology, Center for High-Throughput Biology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
4
1] Schizophrenia Research Institute, Sydney, NSW, Australia [2] The University of Newcastle, Callaghan, NSW, Australia.
5
Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
6
Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia.
7
Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
8
RNA Biology Laboratory, RIKEN Advanced Research Institute, Wako, Saitama, Japan.
9
Isis Pharmaceuticals, Carlsbad, CA, USA.
10
1] Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia [2] Garvan Institute of Medical Research, Sydney, NSW, Australia [3] St Vincent's Clinical School and School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.

Abstract

Schizophrenia (SZ) is a complex disease characterized by impaired neuronal functioning. Although defective alternative splicing has been linked to SZ, the molecular mechanisms responsible are unknown. Additionally, there is limited understanding of the early transcriptomic responses to neuronal activation. Here, we profile these transcriptomic responses and show that long non-coding RNAs (lncRNAs) are dynamically regulated by neuronal activation, including acute downregulation of the lncRNA Gomafu, previously implicated in brain and retinal development. Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. These results functionally link activity-regulated lncRNAs and alternative splicing in neuronal function and suggest that their dysregulation may contribute to neurological disorders.

PMID:
23628989
DOI:
10.1038/mp.2013.45
[Indexed for MEDLINE]

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