Noncoding regions of C. Elegans mRNA undergo selective adenosine to inosine deamination and contain a small number of editing sites per transcript

Emily C. Wheeler, Michael C. Washburn, Francois Major, Douglas B. Rusch, Heather A. Hundley

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

ADARs (Adenosine deaminases that act on RNA) “edit” RNA by converting adenosines to inosines within doublestranded regions. The primary targets of ADARs are long duplexes present within noncoding regions of mRNAs, such as introns and 30 untranslated regions (UTRs). Because adenosine and inosine have different base-pairing properties, editing within these regions can alter splicing and recognition by small RNAs. However, despite numerous studies identifying multiple editing sites in these genomic regions, little is known about the extent to which editing sites cooccur on individual transcripts or the functional output of these combinatorial editing events. To begin to address these questions, we performed an ultra-deep sequencing analysis of 4 Caenorhabditis elegans 30 UTRs that are known ADAR targets. Synchronous editing events were determined for the long duplexes in vivo. Furthermore, the validity of each editing event was confirmed by sequencing the same regions of mRNA from worms that lack A-to-I editing. This analysis identified a large number of editing sites that can occur within each 30 UTR, but interestingly, each individual transcript contained only a small fraction of these A-to-I editing events. In addition, editing patterns were not random, indicating that an editing event can affect the efficiency of editing at subsequent adenosines. Furthermore, we identified specific sites that can be both positively and negatively correlated with additional sites leading to mutually exclusive editing patterns. These results suggest that editing in noncoding regions is selective and hyper-editing of cellular RNAs is rare.

Original languageEnglish (US)
Pages (from-to)162-174
Number of pages13
JournalRNA Biology
Volume12
Issue number2
DOIs
StatePublished - 2015

Keywords

  • ADAR
  • C. elegans
  • Inosine
  • Noncoding
  • RNA editing
  • RNA-seq
  • UTR

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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