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PMID: 27348216 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature neuroscience ·Vol. 19 ·No. 8 ·2016-00-00 ·Pages 1093-9

Hwang T, Park CK, Leung AK, Gao Y, Hyde TM, Kleinman JE, Rajpurohit A, Tao R, Shin JH, Weinberger DR

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.

MeSH Terms
Adenosine/metabolism Adenosine Deaminase/metabolism Brain/growth & development Diagnosis Gene Ontology Humans Inosine/metabolism RNA Editing/genetics RNA-Binding Proteins/genetics,metabolism
Chemicals
RNA-Binding Proteins Inosine Adenosine Deaminase pegademase bovine Adenosine
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Hwang Taeyoung
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.
Park Chul-Kee
Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
Leung Anthony K L
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.
Gao Yuan
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
Hyde Thomas M
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.
Kleinman Joel E
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
Rajpurohit Anandita
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
Tao Ran
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
Shin Joo Heon
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
Weinberger Daniel R
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.
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Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1546-1726
DOI
10.1038/nn.4337
Published
2016-00-00
Epub
2016-00-27
Pages
1093-9
Language
English
Region
United States
NLM ID
9809671
Subset
IM
External Links
PubMed source DOI: 10.1038/nn.4337 View journal details
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