RT Journal
A1 Zhao, Han-Qing
A1 Zhang, Pan
A1 Gao, Hua
A1 He, Xiandong
A1 Dou, Yanmei
A1 Huang, August Y.
A1 Liu, Xi-Ming
A1 Ye, Adam Y.
A1 Dong, Meng-Qiu
A1 Wei, Liping
T1 Profiling the RNA editomes of wild-type C. elegans and ADAR mutants
JF Genome Research 
JO Genome Research 
YR 2015 
FD January 01 
VO 25 
IS 1 
SP 66 
OP 75 
DO 10.1101/gr.176107.114 
UL http://genome.cshlp.org/content/25/1/66.abstract 
AB 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.