A distant cis acting intronic element induces site-selective RNA editing

Nucleic Acids Res. 2012 Oct;40(19):9876-86. doi: 10.1093/nar/gks691. Epub 2012 Jul 30.


Transcripts have been found to be site selectively edited from adenosine-to-inosine (A-to-I) in the mammalian brain, mostly in genes involved in neurotransmission. While A-to-I editing occurs at double-stranded structures, other structural requirements are largely unknown. We have investigated the requirements for editing at the I/M site in the Gabra-3 transcript of the GABA(A) receptor. We identify an evolutionarily conserved intronic duplex, 150 nt downstream of the exonic hairpin where the I/M site resides, which is required for its editing. This is the first time a distant RNA structure has been shown to be important for A-to-I editing. We demonstrate that the element also can induce editing in related but normally not edited RNA sequences. In human, thousands of genes are edited in duplexes formed by inverted repeats in non-coding regions. It is likely that numerous such duplexes can induce editing of coding regions throughout the transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Introns*
  • Mice
  • Nucleic Acid Conformation
  • RNA Editing*
  • RNA Splicing
  • Rats
  • Receptors, GABA-A / genetics
  • Regulatory Sequences, Ribonucleic Acid*
  • Swine


  • Receptors, GABA-A
  • Regulatory Sequences, Ribonucleic Acid