Dynamic regulation of RNA editing in human brain development and disease
Embargo until
2017-05-01
Date
2016-03-23
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Johns Hopkins University
Abstract
RNA editing is increasingly recognized as a molecular mechanism regulating RNA activity and recoding proteins. Here, I surveyed the global landscape of RNA editing in human brain tissues and identify three unique patterns of A-to-I RNA editing 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 in development is most apparent in brain and conserved in mouse brain development. The increasing pattern associates with the growth of cortical layers and neuronal maturation, correlates with mRNA abundance, and influences miRNA binding energy. Gene ontology analyses implicate the increasing pattern in vesicle or organelle membrane-related genes and glutamate signaling pathways. We also show that the increasing pattern is selectively perturbed in spinal cord injury and glioblastoma. Our findings reveal dynamic and functional aspects of RNA editing in brain, providing new insight into epigenetic regulation of sequence diversity.
Description
Keywords
RNA editing, Next generation sequencing, Brain development, RNA-seq