title: Dynamic regulation of RNA editing in human brain development and disease.
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.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Taeyoung
authors.initials: T
authors.lastname: Hwang
authors.affiliation: Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Chul-Kee
authors.initials: CK
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.|Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Anthony K L
authors.initials: AK
authors.lastname: Leung
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.|Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Biological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Hyde
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Joel E
authors.initials: JE
authors.lastname: Kleinman
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Anandita
authors.initials: A
authors.lastname: Rajpurohit
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Joo Heon
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.|Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism*; D001921:Brain / Q000254:growth & development*; D003933:Diagnosis; D063990:Gene Ontology; D006801:Humans; D007288:Inosine / Q000378:metabolism; D017393:RNA Editing / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016601:RNA-Binding Proteins; D007288:Inosine; D000243:Adenosine Deaminase; C051409:pegademase bovine; D000241:Adenosine