| Title | Profiling the RNA editomes of wild-type C. elegans and ADAR mutants |
| Authors | Zhao, Han-Qing Zhang, Pan Gao, Hua He, Xiandong Dou, Yanmei Huang, August Y. Liu, Xi-Ming Ye, Adam Y. Dong, Meng-Qiu Wei, Liping |
| Affiliation | Natl Inst Biol Sci, Beijing 102206, Peoples R China. Peking Univ, Sch Life Sci, Ctr Bioinformat, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China. |
| Keywords | CAENORHABDITIS-ELEGANS MESSENGER-RNA ADENOSINE DEAMINASES EDITING SITES MASS-SPECTRA TARGETS SEQ IDENTIFICATION PATHWAYS QUANTIFICATION |
| Issue Date | 2015 |
| Publisher | genome research |
| Citation | GENOME RESEARCH.2015,25,(1),66-75. |
| 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. |
| URI | http://hdl.handle.net/20.500.11897/188560 |
| ISSN | 1088-9051 |
| DOI | 10.1101/gr.176107.114 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 生命科学学院 |
