ADAR1 controls apoptosis of stressed cells by inhibiting Staufen1-mediated mRNA decay
| Autor: | Kazuko Nishikura, Andrew V. Kossenkov, Chunzi Song, Hsin Yao Tang, David W. Speicher, Emmanuel Skordalakes, Hiromitsu Ota, Jayamanna Wickramasinghe, Louise C. Showe, Masayuki Sakurai, Yusuke Shiromoto |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Gene isoform RNA editing Adenosine Deaminase MAP Kinase Signaling System Alu RNA Stability dsRNA Apoptosis RNA-binding protein Biology Article stress 03 medical and health sciences 0302 clinical medicine mRNA decay Stress Physiological Structural Biology ADAR1 Humans Phosphorylation Molecular Biology Exportin-5 Kinase SMD RNA-Binding Proteins RNA Staufen1 Molecular biology Cell biology Cytoskeletal Proteins RNA silencing 030104 developmental biology Cytoplasm MAP kinase Protein Processing Post-Translational 030217 neurology & neurosurgery |
| Zdroj: | Nature structural & molecular biology |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | Both p150 and p110 isoforms of ADAR1 convert adenosine to inosine in double-stranded RNA (dsRNA). ADAR1p150 suppresses the dsRNA-sensing mechanism that activates MDA5-MAVS-IFN signaling in the cytoplasm. In contrast, the biological function of the ADAR1p110 isoform, which is usually located in the nucleus, is largely unknown. Here, we show that stress-activated phosphorylation of ADAR1p110 by MKK6-p38-MSK MAP kinases promotes its binding to Exportin-5 and its export from the nucleus. After translocating to the cytoplasm, ADAR1p110 suppresses apoptosis in stressed cells by protecting many antiapoptotic gene transcripts that contain 3'-untranslated-region dsRNA structures primarily comprising inverted Alu repeats. ADAR1p110 competitively inhibits binding of Staufen1 to the 3'-untranslated-region dsRNAs and antagonizes Staufen1-mediated mRNA decay. Our study reveals a new stress-response mechanism in which human ADAR1p110 and Staufen1 regulate surveillance of a set of mRNAs required for survival of stressed cells. |
| Databáze: | OpenAIRE |
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