ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins

Aparna Anantharaman, Vidisha Tripathi, Abid Khan, Je Hyun Yoon, Deepak K. Singh, Omid Gholamalamdari, Shuomeng Guang, Johan Ohlson, Helene Wahlstedt, Marie Öhman, Michael F. Jantsch, Nicholas K. Conrad, Jian Ma, Myriam Gorospe, Supriya G. Prasanth, Kannanganattu V. Prasanth

Research output: Contribution to journalArticle

Abstract

Adenosine deaminases acting on RNA (ADARs) catalyze the editing of adenosine residues to inosine (A-to-I) within RNA sequences, mostly in the introns and UTRs (un-translated regions). The significance of editing within non-coding regions of RNA is poorly understood. Here, we demonstrate that association of ADAR2 with RNA stabilizes a subset of transcripts. ADAR2 interacts with and edits the 3Î.,UTR of nuclear-retained Cat2 transcribed nuclear RNA (Ctn RNA). In absence of ADAR2, the abundance and half-life of Ctn RNA are significantly reduced. Furthermore, ADAR2-mediated stabilization of Ctn RNA occurred in an editing-independent manner. Unedited Ctn RNA shows enhanced interaction with the RNA-binding proteins HuR and PARN [Poly(A) specific ribonuclease deadenylase]. HuR and PARN destabilize Ctn RNA in absence of ADAR2, indicating that ADAR2 stabilizes Ctn RNA by antagonizing its degradation by PARN and HuR. Transcriptomic analysis identified other RNAs that are regulated by a similar mechanism. In summary, we identify a regulatory mechanism whereby ADAR2 enhances target RNA stability by limiting the interaction of RNA-destabilizing proteins with their cognate substrates.

Original languageEnglish (US)
Pages (from-to)4189-4201
Number of pages13
JournalNucleic acids research
Volume45
Issue number7
DOIs
StatePublished - Apr 20 2017

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ASJC Scopus subject areas

  • Genetics

Cite this

Anantharaman, A., Tripathi, V., Khan, A., Yoon, J. H., Singh, D. K., Gholamalamdari, O., Guang, S., Ohlson, J., Wahlstedt, H., Öhman, M., Jantsch, M. F., Conrad, N. K., Ma, J., Gorospe, M., Prasanth, S. G., & Prasanth, K. V. (2017). ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins. Nucleic acids research, 45(7), 4189-4201. https://doi.org/10.1093/nar/gkw1304