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Nat Commun. 2017 Nov 13;8(1):1440. doi: 10.1038/s41467-017-01458-8.

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

Author information

1
Cancer Research Center, Sheba Medical Center, Tel Hashomer, 52621, Ramat-Gan, Israel.
2
The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel Hashomer, 52621, Ramat-Gan, Israel.
3
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, 52900, Ramat-Gan, Israel.
4
Department of Molecular Genetics, Weizmann Institute of Science, 76100, Rehovot, Israel.
5
Sackler School of Medicine, Tel Aviv University, 69978, Tel-Aviv, Israel.
6
Cancer Research Center, Sheba Medical Center, Tel Hashomer, 52621, Ramat-Gan, Israel. Eran.Eyal@sheba.health.gov.il.
7
The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel Hashomer, 52621, Ramat-Gan, Israel. Eran.Eyal@sheba.health.gov.il.
8
Cancer Research Center, Sheba Medical Center, Tel Hashomer, 52621, Ramat-Gan, Israel. Gidi.rechavi@sheba.health.gov.il.
9
The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel Hashomer, 52621, Ramat-Gan, Israel. Gidi.rechavi@sheba.health.gov.il.
10
Sackler School of Medicine, Tel Aviv University, 69978, Tel-Aviv, Israel. Gidi.rechavi@sheba.health.gov.il.

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.

PMID:
29129909
PMCID:
PMC5682290
DOI:
10.1038/s41467-017-01458-8
[Indexed for MEDLINE]
Free PMC Article

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