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

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

Author information

1
National Institute of Biological Sciences, Beijing 102206, China;
2
Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
3
National Institute of Biological Sciences, Beijing 102206, China; weilp@mail.cbi.pku.edu.cn dongmengqiu@nibs.ac.cn.
4
National Institute of Biological Sciences, Beijing 102206, China; Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China weilp@mail.cbi.pku.edu.cn dongmengqiu@nibs.ac.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. 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.

PMID:
25373143
PMCID:
PMC4317174
DOI:
10.1101/gr.176107.114
[Indexed for MEDLINE]
Free PMC Article

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