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

G. Barry, J. A. Briggs, D. P. Vanichkina, E. M. Poth, N. J. Beveridge, V. S. Ratnu, S. P. Nayler, K. Nones, J. Hu, T. W. Bredy, S. Nakagawa, F. Rigo, R. J. Taft, M. J. Cairns, S. Blackshaw, E. J. Wolvetang, J. S. Mattick

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)486-494
Number of pages9
JournalMolecular psychiatry
Volume19
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • Alternative splicing
  • Gomafu
  • Neuronal activation
  • Quaking homolog
  • Schizophrenia

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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