Structure-mediated modulation of mRNA abundance by A-to-I editing

Nat Commun. 2017 Nov 2;8(1):1255. doi: 10.1038/s41467-017-01459-7.


RNA editing introduces single nucleotide changes to RNA, thus potentially diversifying gene expression. Recent studies have reported significant changes in RNA editing profiles in disease and development. The functional consequences of these widespread alterations remain elusive because of the unknown function of most RNA editing sites. Here, we carry out a comprehensive analysis of A-to-I editomes in human populations. Surprisingly, we observe highly similar editing profiles across populations despite striking differences in the expression levels of ADAR genes. Striving to explain this discrepancy, we uncover a functional mechanism of A-to-I editing in regulating mRNA abundance. We show that A-to-I editing stabilizes RNA secondary structures and reduces the accessibility of AGO2-miRNA to target sites in mRNAs. The editing-dependent stabilization of mRNAs in turn alters the observed editing levels in the stable RNA repertoire. Our study provides valuable insights into the functional impact of RNA editing in human cells.

Publication types

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

MeSH terms

  • Adenosine / metabolism
  • Adenosine Deaminase / genetics*
  • Argonaute Proteins / genetics*
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Hep G2 Cells
  • Humans
  • Inosine / metabolism
  • K562 Cells
  • MicroRNAs / metabolism
  • RNA Editing / genetics*
  • RNA Stability*
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics*


  • AGO2 protein, human
  • Argonaute Proteins
  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins
  • Inosine
  • ADAR protein, human
  • ADARB1 protein, human
  • ADARB2 protein, human
  • Adenosine Deaminase
  • Adenosine