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

Oz Solomon, Ayelet 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 () and Gidi Rechavi ()
Additional contact information
Oz Solomon: Sheba Medical Center, Tel Hashomer
Ayelet Segni: Sheba Medical Center, Tel Hashomer
Karen Cesarkas: Sheba Medical Center, Tel Hashomer
Hagit T. Porath: Bar-Ilan University
Victoria Marcu-Malina: Sheba Medical Center, Tel Hashomer
Orel Mizrahi: Weizmann Institute of Science
Noam Stern-Ginossar: Weizmann Institute of Science
Nitzan Kol: Sheba Medical Center, Tel Hashomer
Sarit Farage-Barhom: Sheba Medical Center, Tel Hashomer
Efrat Glick-Saar: Sheba Medical Center, Tel Hashomer
Yaniv Lerenthal: Sheba Medical Center, Tel Hashomer
Erez Y. Levanon: Bar-Ilan University
Ninette Amariglio: Sheba Medical Center, Tel Hashomer
Ron Unger: Bar-Ilan University
Itamar Goldstein: Sheba Medical Center, Tel Hashomer
Eran Eyal: Sheba Medical Center, Tel Hashomer
Gidi Rechavi: Sheba Medical Center, Tel Hashomer

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01458-8

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