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.