Dynamic regulation of RNA editing in human brain development and disease

Taeyoung Hwang, Chul Kee Park, Anthony Kar Lun Leung, Yuan Gao, Thomas Hyde, Joel Kleinman, Anandita Rajpurohit, Ran Tao, Joo Heon Shin, Daniel Weinberger

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1093-1099
Number of pages7
JournalNature Neuroscience
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2016

ASJC Scopus subject areas

  • Neuroscience(all)

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