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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Animals
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Electrophoretic Mobility Shift Assay
  • Embryo, Mammalian
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Gene Expression Regulation*
  • Humans
  • Immunoprecipitation
  • Mice
  • Mice, Inbred C57BL
  • Microarray Analysis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Oligonucleotides, Antisense / pharmacology
  • Proteome
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Receptor, ErbB-4
  • Schizophrenia / genetics*
  • Serine-Arginine Splicing Factors


  • DISC1 protein, human
  • Miat long non-coding RNA
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Oligonucleotides, Antisense
  • Proteome
  • QKI protein, human
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • Serine-Arginine Splicing Factors
  • ERBB4 protein, human
  • ErbB Receptors
  • Erbb4 protein, mouse
  • Receptor, ErbB-4