Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways

Nat Commun. 2015 Mar 9;6:6355. doi: 10.1038/ncomms7355.

Abstract

Adenosine deaminases acting on RNA (ADARs) are the primary factors underlying adenosine to inosine (A-to-I) editing in metazoans. Here we report the first global study of ADAR1-RNA interaction in human cells using CLIP-seq. A large number of CLIP sites are observed in Alu repeats, consistent with ADAR1's function in RNA editing. Surprisingly, thousands of other CLIP sites are located in non-Alu regions, revealing functional and biophysical targets of ADAR1 in the regulation of alternative 3' UTR usage and miRNA biogenesis. We observe that binding of ADAR1 to 3' UTRs precludes binding by other factors, causing 3' UTR lengthening. Similarly, ADAR1 interacts with DROSHA and DGCR8 in the nucleus and possibly out-competes DGCR8 in primary miRNA binding, which enhances mature miRNA expression. These functions are dependent on ADAR1's editing activity, at least for a subset of targets. Our study unfolds a broad landscape of the functional roles of ADAR1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Deaminase / genetics*
  • Adenosine Deaminase / metabolism*
  • Base Sequence
  • Cell Fractionation
  • Cell Line
  • DNA Primers / genetics
  • Humans
  • Immunoprecipitation
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Protein Binding / genetics
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism*
  • Ribonuclease III / metabolism
  • Sequence Analysis, RNA

Substances

  • DGCR8 protein, human
  • DNA Primers
  • MicroRNAs
  • RNA-Binding Proteins
  • DROSHA protein, human
  • Ribonuclease III
  • ADAR protein, human
  • Adenosine Deaminase

Associated data

  • GEO/GSE55363