Profiling the RNA editomes of wild-type C. elegans and ADAR mutants
- Han-Qing Zhao1,
- Pan Zhang1,
- Hua Gao2,
- Xiandong He1,
- Yanmei Dou2,
- August Yue Huang1,
- Ximing Liu1,
- Adam Yongxin Ye2,
- Meng-Qiu Dong1 and
- Liping Wei1,3
- ↵* Corresponding author; email: weilp{at}mail.cbi.pku.edu.cn
Abstract
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. C. 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 the wild type and ADAR mutants. We developed a new computational pipeline with a 'bisulfite-seq-mapping-like' step and achieved a 3-fold increase in identification sensitivity. 99.5% of the 47,660 A-to-I editing sites were found in clusters. Of the 3,080 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 its number of editing sites within it. Intriguingly, for 80% of the clusters with ten 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 revealed a sophisticated landscape of RNA editing and distinct modes of action of different ADARs.
- Received March 25, 2014.
- Accepted October 29, 2014.
- Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International license), as described at http://creativecommons.org/licenses/by-nc/4.0/.
