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

Soh Ishiguro, Josephine Galipon, Rintaro Ishii, Yutaka Suzuki, Shinji Kondo, Mariko Okada-Hatakeyama, Masaru Tomita, Kumiko Ui-Tei

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
JournalRNA Biology
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

MicroRNAs
Base Pairing
Enzymes
Adenosine Deaminase
RNA
Protein Isoforms
RNA Editing
RNA Isoforms
Inosine
Deamination
Nucleotide Motifs
Double-Stranded RNA
Gene Silencing
Immunoprecipitation
Adenosine
Seeds
Genome
Genes

Keywords

  • ADAR
  • binding preference
  • double-stranded RNA binding protein
  • miRNA
  • miRNA manqué
  • RIP-seq
  • RNA editing

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

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. / Ishiguro, Soh; Galipon, Josephine; Ishii, Rintaro; Suzuki, Yutaka; Kondo, Shinji; Okada-Hatakeyama, Mariko; Tomita, Masaru; Ui-Tei, Kumiko.

In: RNA Biology, 01.01.2018.

Research output: Contribution to journalArticle

Ishiguro, Soh ; Galipon, Josephine ; Ishii, Rintaro ; Suzuki, Yutaka ; Kondo, Shinji ; Okada-Hatakeyama, Mariko ; Tomita, Masaru ; Ui-Tei, Kumiko. / 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. In: RNA Biology. 2018.
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