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

• DOI: 10.1038/s41467-017-01458-8
• Publication Date: 2017-11-07T10:22:55Z
• Authors: Oz Solomon; Ayelet Di Segni; Karen Cesarkas; Hagit T. Porath; Victoria Marcu-Ma...; 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
• Keywords: RNA Silencing; ADAR; Nucleic acid structure; Riboswitch; Guide RNA

Adenosine deaminase acting on RNA 1 (ADAR1) is the master editor, catalyzing deamination of adenosine to inosine. editing vital for preventing abnormal activation cytosolic nucleic acid sensing pathways by self-double-stranded RNAs. Here we determine, parallel analysis secondary structure sequencing (PARS-seq), global changes in ADAR1 deficient cells. Surprisingly, silencing resulted a lower double-stranded single-stranded ratio, suggesting that A-to-I can stabilize large subset imperfect duplexes. The duplexes destabilized are composed vastly complementary inverted Alus found untranslated regions genes performing biological processes, including housekeeping functions and type-I interferon responses. They predominantly cytoplasmic generally demonstrate higher ribosomal occupancy. Our findings imply effect context dependent underline intricate regulatory role structure.