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

FEBS Lett. 2017 Sep;591(18):2890-2904. doi: 10.1002/1873-3468.12795. Epub 2017 Aug 30.

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.

Keywords: ADAR; Ctn RNA; HuR; RNA editing; breast cancer; mRNA stability.

Publication types

  • Letter

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adenosine Deaminase / genetics
  • Adenosine Deaminase / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Humans
  • Immunoprecipitation
  • RNA Editing / genetics*
  • RNA Stability / genetics
  • RNA Stability / physiology*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*

Substances

  • 3' Untranslated Regions
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • ADAR protein, human
  • ADARB1 protein, human
  • Adenosine Deaminase