Base-pairing probability in the microRNA stem region affects the binding and editing specificity of human A-to-I editing enzymes ADAR1-p110 and ADAR2. Issue 7 (3rd July 2018)

• Record Type: Journal Article
• Authors: Ishiguro, Soh; Galipon, Josephine; Ishii, Rintaro; Suzuki, Yutaka; Kondo, Shinji; Okada-Hatakeyama, Mariko; Tomita, Masaru; Ui-Tei, Kumiko
• Is Part Of: RNA biology. Volume 15:Issue 7(2018)
• Page Start: 976
• Page End: 989
• Publication Date: 2018-07-03
• Subjects: ADAR -- double-stranded RNA binding protein -- binding preference -- RNA editing -- miRNA -- miRNA manqué -- RIP-seq; RNA -- Periodicals; Molecular biology -- Periodicals; Molecular biology; RNA; Periodicals; 572.8805
• DOI: 10.1080/15476286.2018.1486658
• Languages: English
• ISSNs: 1547-6286

Abstract

ABSTRACT: Adenosine deaminases acting on RNA (ADARs) catalyze the deamination of adenosine (A) to inosine (I). A-to-I RNA editing targets double-stranded RNA (dsRNA), and increases the complexity of gene regulation by modulating base pairing-dependent processes such as splicing, translation, and microRNA (miRNA)-mediated gene silencing. This study investigates the genome-wide binding preferences of the nuclear constitutive isoforms ADAR1-p110 and ADAR2 on human miRNA species by RNA immunoprecipitation of ADAR-bound small RNAs (RIP-seq). Our results suggest that secondary structure predicted by base-pairing probability in the mainly double-stranded region of a pre-miRNA or mature miRNA duplex may determine ADAR isoform preference for binding distinct subpopulations of miRNAs. Furthermore, we identify 31 unique editing sites with statistical significance, 19 sites of which are novel editing sites. Editing sites are enriched in the seed region responsible for target recognition by miRNAs, and isoform-specific nucleotide motifs in the immediate vicinity and opposite of editing sites are consistent with previous studies, and further reveal that ADAR2 may edit A/C bulges more frequently than ADAR1-p110 in the context of miRNA.