title: Functional Impact of RNA editing and ADARs on regulation of gene expression: perspectives from deep sequencing studies.
abstract: Cells regulate gene expression at multiple levels leading to a balance between robustness and complexity within their proteome. One core molecular step contributing to this important balance during metazoan gene expression is RNA editing, such as the co-transcriptional recoding of RNA transcripts catalyzed by the adenosine deaminse acting on RNA (ADAR) family of enzymes. Understanding of the adenosine-to-inosine RNA editing process has been broadened considerably by the next generation sequencing (NGS) technology, which allows for in-depth demarcation of an RNA editome at nucleotide resolution. However, critical issues remain unresolved with regard to how RNA editing cooperates with other transcript-associated events to underpin regulated gene expression. Here we review the growing body of evidence, provided by recent NGS-based studies, that links RNA editing to other mechanisms of post-transcriptional RNA processing and gene expression regulation including alternative splicing, transcript stability and localization, and the biogenesis and function of microRNAs (miRNAs). We also discuss the possibility that systematic integration of NGS data may be employed to establish the rules of an "RNA editing code", which may give us new insights into the functional consequences of RNA editing.
authors.affiliation: Graduate Institute of Biomedical Sciences, Tao-Yuan, Taiwan ; Department of Biochemistry, Tao-Yuan, Taiwan ; Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Hsuan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Graduate Institute of Biomedical Sciences, Tao-Yuan, Taiwan.
authors.forename: Chung-Pei
authors.initials: CP
authors.lastname: Ma
authors.affiliation: Graduate Institute of Biomedical Sciences, Tao-Yuan, Taiwan.
authors.forename: Yi-Tung
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Sciences, Tao-Yuan, Taiwan ; Department of Biomedical Sciences, College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Schuyler
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan ; Department of Otolaryngology, Chang Gung Memorial Hospital at Lin-Kuo, Tao-Yuan, Taiwan.
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Chang
authors.affiliation: Graduate Institute of Biomedical Sciences, Tao-Yuan, Taiwan ; Department of Biomedical Sciences, College of Medicine, Tao-Yuan, Taiwan ; Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Bertrand Chin-Ming
authors.initials: BC
authors.lastname: Tan
keywords: ADAR; Alternative splicing; Gene regulation; MicroRNA; Next generation sequencing (NGS); RNA editing; RNA-seq; Small RNA-seq; Transcriptional regulation