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Published (Version of record)CC BY V4.0, Open Access
Journal article
RNA editing by ADAR1 leads to context-dependent transcriptome-wide changes in RNA secondary structure
Nature Communications, Vol.8, 1440 (2017)
13/Nov/2017
Abstract
Adenosine deaminase acting on RNA 1 (ADAR1) is the master RNA editor, catalyzing the deamination of adenosine to inosine. RNA editing is vital for preventing abnormal activation of cytosolic nucleic acid sensing pathways by self-double-stranded RNAs. Here we determine, by parallel analysis of RNA secondary structure sequencing (PARS-seq), the global RNA secondary structure changes in ADAR1 deficient cells. Surprisingly, ADAR1 silencing resulted in a lower global double-stranded to single-stranded RNA ratio, suggesting that A-to-I editing can stabilize a large subset of imperfect RNA duplexes. The duplexes destabilized by editing are composed of vastly complementary inverted Alus found in untranslated regions of genes performing vital biological processes, including housekeeping functions and type-I interferon responses. They are predominantly cytoplasmic and generally demonstrate higher ribosomal occupancy. Our findings imply that the editing effect on RNA secondary structure is context dependent and underline the intricate regulatory role of ADAR1 on global RNA secondary structure.
Details
- Title
- RNA editing by ADAR1 leads to context-dependent transcriptome-wide changes in RNA secondary structure
- Creators
- Oz Solomon (null)Ayelet Di Segni (null)Karen Cesarkas (null)Hagit T. Porath (null)Victoria Marcu-Malina (null)Orel Mizrahi (null) - 972WIS_INST___111Noam Stern-Ginossar (null) - 972WIS_INST___111Nitzan Kol (null)Sarit Farage-Barhom (null)Efrat Glick-Saar (null) - The Weizmann Institute of ScienceYaniv Lerenthal (null)Erez Y. Levanon (null)Ninette Amariglio (null)Ron Unger (null)Itamar Goldstein (null)Eran Eyal (null)Gidi Rechavi (null)
- Resource Type
- Journal article
- Publication Details
- Nature Communications, Vol.8, 1440 (2017); 13/Nov/2017
- Number of pages
- 14
- Language
- English
- DOI
- https://doi.org/10.1038/s41467-017-01458-8
- Grant note
- We thank Eran Segal, Howard Chang and Yue Wan for their useful advice regarding the PARS-seq protocol. We thank Mali Salmon-Divon for useful advice regarding the splicing analysis. We thank Tirza Doniger for helping us with the data. The work of O.S. was done in partial fulfillment of the requirements of the Faculty of Life-Sciences, Bar-Ilan University, Israel. this work was supported by the Varda and Boaz Dotan Research Center in Hemato-oncology affiliated to the Tel Aviv University, the Canadian Institute of Health Research joint Canada-Israel health research Grant No. 108188-001, the Flight Attendant Medical Research Institute (FAMRI), Israeli Centers of Research Excellence (I-CORE), ISF Gene Regulation in Complex Human Disease Center, ISF Chromatin and RNA Gene Regulation Center. G.R. holds the Djerassi Chair in Oncology, Tel Aviv University, Israel. Author contributions O.S. performed the bioinformatic, structural and statistical assays, analyzed the data, and wrote the manuscript. A.D.S. and K.C. preformed siRNA and nuclease assays, prepared the PARS-seq libraries, and wrote the manuscript. H.T.P. and E.Y.L. preformed the hyper-editing analysis. V.-M.M. preformed the siRNA assays and prepared the Ribo-seq samples. O.M. and N.S.-G. preformed the Ribo-seq experiment. N.K. performed bioinformatics analysis. S.F.-B. and E.G.-S. helped in the preparation of the PARS-seq libraries. Y.L. preformed the RNA-seq and Ribo-seq experiments. N.A. and R.U. conceived ideas and helped writing the manuscript. I.G. helped with the functional bioinformatics and participated in writing the manuscript. E.E. and G.R. designed the experiments, analyzed the data, conceived ideas and wrote the article.
- Record Identifier
- 993264619703596
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