title: A biochemical landscape of A-to-I RNA editing in the human brain transcriptome.
abstract: Inosine is an abundant RNA modification in the human transcriptome and is essential for many biological processes in modulating gene expression at the post-transcriptional level. Adenosine deaminases acting on RNA (ADARs) catalyze the hydrolytic deamination of adenosines to inosines (A-to-I editing) in double-stranded regions. We previously established a biochemical method called "inosine chemical erasing" (ICE) to directly identify inosines on RNA strands with high reliability. Here, we have applied the ICE method combined with deep sequencing (ICE-seq) to conduct an unbiased genome-wide screening of A-to-I editing sites in the transcriptome of human adult brain. Taken together with the sites identified by the conventional ICE method, we mapped 19,791 novel sites and newly found 1258 edited mRNAs, including 66 novel sites in coding regions, 41 of which cause altered amino acid assignment. ICE-seq detected novel editing sites in various repeat elements as well as in short hairpins. Gene ontology analysis revealed that these edited mRNAs are associated with transcription, energy metabolism, and neurological disorders, providing new insights into various aspects of human brain functions.
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, Tokyo 113-8656, Japan;
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakurai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ueda
authors.forename: Takanori
authors.initials: T
authors.lastname: Yano
authors.forename: Shunpei
authors.initials: S
authors.lastname: Okada
authors.forename: Hideki
authors.initials: H
authors.lastname: Terajima
authors.forename: Toutai
authors.initials: T
authors.lastname: Mitsuyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Toyoda
authors.forename: Asao
authors.initials: A
authors.lastname: Fujiyama
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kawabata
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000241:Adenosine / Q000235:genetics*; D000328:Adult; D001921:Brain / Q000378:metabolism*; D002877:Chromosomes, Human; D004734:Energy Metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007288:Inosine / Q000235:genetics*; D008957:Models, Genetic; D009422:Nervous System Diseases / Q000235:genetics; D017393:RNA Editing; D012333:RNA, Messenger / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic; D059467:Transcriptome / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D007288:Inosine; D000241:Adenosine