Complex regulation of ADAR-mediated RNA-editing across tissues

BMC Genomics. 2016 Jan 15:17:61. doi: 10.1186/s12864-015-2291-9.

Abstract

Background: RNA-editing is a tightly regulated, and essential cellular process for a properly functioning brain. Dysfunction of A-to-I RNA editing can have catastrophic effects, particularly in the central nervous system. Thus, understanding how the process of RNA-editing is regulated has important implications for human health. However, at present, very little is known about the regulation of editing across tissues, and individuals.

Results: Here we present an analysis of RNA-editing patterns from 9 different tissues harvested from a single mouse. For comparison, we also analyzed data for 5 of these tissues harvested from 15 additional animals. We find that tissue specificity of editing largely reflects differential expression of substrate transcripts across tissues. We identified a surprising enrichment of editing in intronic regions of brain transcripts, that could account for previously reported higher levels of editing in brain. There exists a small but remarkable amount of editing which is tissue-specific, despite comparable expression levels of the edit site across multiple tissues. Expression levels of editing enzymes and their isoforms can explain some, but not all of this variation.

Conclusions: Together, these data suggest a complex regulation of the RNA-editing process beyond transcript expression levels.

MeSH terms

  • Adenosine Deaminase / biosynthesis
  • Adenosine Deaminase / genetics*
  • Animals
  • Brain / growth & development
  • Brain / metabolism
  • Gene Expression Regulation
  • Humans
  • Introns / genetics
  • Mice
  • Organ Specificity / genetics*
  • Protein Isoforms / genetics
  • RNA Editing / genetics*
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics*
  • Transcription, Genetic

Substances

  • Protein Isoforms
  • RNA-Binding Proteins
  • ADAR1 protein, mouse
  • ADAR2 protein, mouse
  • Adenosine Deaminase