Profiling the RNA editomes of wild-type C. elegans and ADAR mutants

Genome Res. 2015 Jan;25(1):66-75. doi: 10.1101/gr.176107.114. Epub 2014 Nov 4.


RNA editing increases transcriptome diversity through post-transcriptional modifications of RNA. Adenosine deaminases that act on RNA (ADARs) catalyze the adenosine-to-inosine (A-to-I) conversion, the most common type of RNA editing in higher eukaryotes. Caenorhabditis elegans has two ADARs, ADR-1 and ADR-2, but their functions remain unclear. Here, we profiled the RNA editomes of C. elegans at different developmental stages of wild-type and ADAR mutants. We developed a new computational pipeline with a "bisulfite-seq-mapping-like" step and achieved a threefold increase in identification sensitivity. A total of 99.5% of the 47,660 A-to-I editing sites were found in clusters. Of the 3080 editing clusters, 65.7% overlapped with DNA transposons in noncoding regions and 73.7% could form hairpin structures. The numbers of editing sites and clusters were highest at the L1 and embryonic stages. The editing frequency of a cluster positively correlated with the number of editing sites within it. Intriguingly, for 80% of the clusters with 10 or more editing sites, almost all expressed transcripts were edited. Deletion of adr-1 reduced the editing frequency but not the number of editing clusters, whereas deletion of adr-2 nearly abolished RNA editing, indicating a modulating role of ADR-1 and an essential role of ADR-2 in A-to-I editing. Quantitative proteomics analysis showed that adr-2 mutant worms altered the abundance of proteins involved in aging and lifespan regulation. Consistent with this finding, we observed that worms lacking RNA editing were short-lived. Taken together, our results reveal a sophisticated landscape of RNA editing and distinct modes of action of different ADARs.

Publication types

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

MeSH terms

  • Adenosine / genetics
  • Adenosine Deaminase / genetics*
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Chromosome Mapping
  • Computational Biology
  • DNA Transposable Elements / genetics
  • Evaluation Studies as Topic
  • Gene Deletion
  • Genetic Association Studies
  • Molecular Sequence Data
  • Multigene Family
  • Nucleic Acid Conformation
  • Polynucleotide Adenylyltransferase / genetics
  • Polynucleotide Adenylyltransferase / metabolism
  • Proteomics
  • RNA Editing*
  • RNA, Helminth / genetics*
  • Sequence Analysis, RNA
  • Transcriptome


  • Caenorhabditis elegans Proteins
  • DNA Transposable Elements
  • RNA, Helminth
  • GLD-2 protein, C elegans
  • Polynucleotide Adenylyltransferase
  • Adenosine Deaminase
  • Adenosine

Associated data

  • SRA/SRP028863