RNA-editing enzymes ADAR1 and ADAR2 coordinately regulate the editing and expression of Ctn RNA

Aparna Anantharaman, Omid Gholamalamdari, Abid Khan, Je Hyun Yoon, Michael F. Jantsch, Jochen C. Hartner, Myriam Gorospe, Supriya G. Prasanth, Kannanganattu V. Prasanth

Research output: Contribution to journalArticlepeer-review

Abstract

Adenosine deaminases acting on RNA (ADARs) are proteins that catalyse widespread A-to-I editing within RNA sequences. We recently reported that ADAR2 edits and stabilizes nuclear-retained Cat2 transcribed nuclear RNA (Ctn RNA). Here, we report that ADAR1 coordinates with ADAR2 to regulate editing and stability of Ctn RNA. We observe an RNA-dependent interaction between ADAR1 and ADAR2. Furthermore, ADAR1 negatively regulates interaction of Ctn RNA with RNA-destabilizing proteins. We also show that breast cancer (BC) cells display elevated ADAR1 but not ADAR2 levels, compared to nontumourigenic cells. Additionally, BC patients with elevated levels of ADAR1 show low survival. Our findings provide insights into overlapping substrate preferences of ADARs and potential involvement of ADAR1 in BC.

Original languageEnglish (US)
Pages (from-to)2890-2904
Number of pages15
JournalFEBS Letters
Volume591
Issue number18
DOIs
StatePublished - Sep 2017

Keywords

  • ADAR
  • Ctn RNA
  • HuR
  • RNA editing
  • breast cancer
  • mRNA stability

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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