RNA editing by ADAR1 leads to context-dependent transcriptome-wide changes in RNA secondary structure

Oz Solomon, Ayelet Di Segni, Karen Cesarkas, Hagit T. Porath, Victoria Marcu-Malina, Orel Mizrahi, Noam Stern-Ginossar, Nitzan Kol, Sarit Farage-Barhom, Efrat Glick-Saar, Yaniv Lerenthal, Erez Y. Levanon, Ninette Amariglio, Ron Unger, Itamar Goldstein, Eran Eyal, Gidi Rechavi

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

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.

Original languageEnglish
Article number1440
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - 13 Nov 2017

Bibliographical note

Publisher Copyright:
© 2017 The Author(s).

Funding

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.

FundersFunder number
ISF Chromatin
ISF Gene Regulation in Complex Human Disease Center
Flight Attendant Medical Research Institute
Canadian Institutes of Health Research108188-001
Tel Aviv University
Israeli Centers for Research Excellence
Varda and Boaz Dotan Research Center for Hemato-Oncology Research, Tel Aviv University

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