Dynamic regulation of RNA editing in human brain development and disease.

Journal: Nature neuroscience
PMID: 27348216

Abstract

RNA editing is increasingly recognized as a molecular mechanism regulating RNA activity and recoding proteins. Here we surveyed the global landscape of RNA editing in human brain tissues and identified three unique patterns of A-to-I RNA editing rates during cortical development: stable high, stable low and increasing. RNA secondary structure and the temporal expression of adenosine deaminase acting on RNA (ADAR) contribute to cis- and trans-regulatory mechanisms of these RNA editing patterns, respectively. Interestingly, the increasing pattern was associated with neuronal maturation, correlated with mRNA abundance and potentially influenced miRNA binding energy. Gene ontology analyses implicated the increasing pattern in vesicle or organelle membrane-related genes and glutamate signaling pathways. We also found that the increasing pattern was selectively perturbed in spinal cord injury and glioblastoma. Our findings reveal global and dynamic aspects of RNA editing in brain, providing new insight into epitranscriptional regulation of sequence diversity.

Authors

  • Taeyoung Hwang
    Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Chul-Kee Park
    Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Anthony K L Leung
    Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
  • Yuan Gao
    Engineering Research Center of EMR and Intelligent Expert System, Ministry of Education, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou Zhejiang Province, China.
  • Thomas M Hyde
    Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
  • Joel E Kleinman
    Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
  • Anandita Rajpurohit
    Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
  • Ran Tao
    Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
  • Joo Heon Shin
    Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
  • Daniel R Weinberger
    Genes, Cognition, and Psychosis Program, National Institute of Mental Health, National Institutes of HealthBethesda, MD, USA; The Lieber Institute for Brain DevelopmentBaltimore, MD, USA; Departments of Psychiatry, Neurology and Neuroscience, Johns Hopkins University School of MedicineBaltimore, MD, USA; The Institute of Genetic Medicine, Johns Hopkins University School of MedicineBaltimore, MD, USA.

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