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

Barry, Guy, Briggs, J. A., Vanichkina, D. P., Poth, E. M., Beveridge, N. J., Vikram Ratnu, Nayler, S. P., Nones, K., Hu, J., Timothy Bredy, Nakagawa, S., Rigo, F., Taft, R. J., Cairns, M. J., Blackshaw, S., Wolvetang, E. J. and Mattick, J. S. (2013) The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Molecular Psychiatry, 19 4: 486-494. doi:10.1038/mp.2013.45


Author Barry, Guy
Briggs, J. A.
Vanichkina, D. P.
Poth, E. M.
Beveridge, N. J.
Vikram Ratnu
Nayler, S. P.
Nones, K.
Hu, J.
Timothy Bredy
Nakagawa, S.
Rigo, F.
Taft, R. J.
Cairns, M. J.
Blackshaw, S.
Wolvetang, E. J.
Mattick, J. S.
Title The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1359-4184
1476-5578
Publication date 2013
Sub-type Article (original research)
DOI 10.1038/mp.2013.45
Open Access Status
Volume 19
Issue 4
Start page 486
End page 494
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing
Collection year 2014
Language eng
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 30 April 2013.

 
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Created: Mon, 05 Aug 2013, 08:56:24 EST by Debra McMurtrie on behalf of Queensland Brain Institute