期刊
MOLECULAR PSYCHIATRY
卷 19, 期 4, 页码 486-494出版社
SPRINGERNATURE
DOI: 10.1038/mp.2013.45
关键词
alternative splicing; Gomafu; neuronal activation; quaking homolog; schizophrenia
资金
- University of Sydney
- National Health and Medical Research Council of Australia
- NSW Department of Health
- National Health and Medical Research Council [631668, APP1023127]
- Discovery Project grant from the Australian Research Council [DP120100729]
- NHMRC Project Grant [631057]
- Schizophrenia Research Institute
- MC Ainsworth Research Fellowship in Epigenetics
- Australia Research Council Discovery Early Career Researcher Award
- ANZ Trustees Scholarship for Medical Research
- Australian Research Council [DP1096148]
- National Institute of Alcohol Abuse and Alcoholism
- National Institutes of Health
- Grants-in-Aid for Scientific Research [21228003, 26113005] Funding Source: KAKEN
- Office Of The Director
- Office Of Internatl Science &Engineering [1014626] Funding Source: National Science Foundation
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 (IncRNAs) are dynamically regulated by neuronal activation, including acute downregulation of the IncRNA 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.
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