Profiling the RNA editomes of wild-type C. elegans and ADAR mutants.
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.
National Institute of Biological Sciences, Beijing 102206, China;
Han-Qing
HQ
Zhao
National Institute of Biological Sciences, Beijing 102206, China;
Pan
P
Zhang
Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
Hua
H
Gao
National Institute of Biological Sciences, Beijing 102206, China;
Xiandong
X
He
Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
Yanmei
Y
Dou
National Institute of Biological Sciences, Beijing 102206, China;
August Y
AY
Huang
National Institute of Biological Sciences, Beijing 102206, China;
Xi-Ming
XM
Liu
Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
Adam Y
AY
Ye
National Institute of Biological Sciences, Beijing 102206, China; weilp@mail.cbi.pku.edu.cn dongmengqiu@nibs.ac.cn.
Meng-Qiu
MQ
Dong
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.
Liping
L
Wei
D000241:Adenosine / Q000235:genetics; D000243:Adenosine Deaminase / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping; D019295:Computational Biology; D004251:DNA Transposable Elements / Q000235:genetics; D005069:Evaluation Studies as Topic; D017353:Gene Deletion; D056726:Genetic Association Studies; D008969:Molecular Sequence Data; D005810:Multigene Family; D009690:Nucleic Acid Conformation; D011062:Polynucleotide Adenylyltransferase / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D017393:RNA Editing; D018510:RNA, Helminth / Q000235:genetics*; D017423:Sequence Analysis, RNA; D059467:Transcriptome
D029742:Caenorhabditis elegans Proteins; D004251:DNA Transposable Elements; D018510:RNA, Helminth; C491056:GLD-2 protein, C elegans; D011062:Polynucleotide Adenylyltransferase; D000243:Adenosine Deaminase; D000241:Adenosine