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| Status |
Public on Mar 21, 2017 |
| Title |
ADAR1 controls apoptosis of stressed cells by inhibiting Staufen-mediated mRNA decay |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Both p150 and p110 isoforms of ADAR1 convert adenosine to inosine in double-stranded RNA (dsRNA). The p150 isoform suppresses the dsRNA sensing mechanism that activates the interferon induction mediated by the MDA5-MAVS signaling. In contrast, the biological function of the p110 isoform localized in the nucleus remains largely unknown. Here we show that stress-activated phosphorylation of ADAR1p110 by MKK6/p38 MAP kinases promotes its binding to Exportin-5 and nuclear export to the cytoplasm. Once translocated to the cytoplasmic, ADAR1p110 suppresses apoptosis of stressed cells by protecting many anti-apoptotic gene transcripts that contain 3’UTR dsRNA structures such as those consisting of inverted Alu repeats. ADAR1p110 competitively inhibits binding of Staufen1 to the 3’UTR dsRNAs and antagonizes the Staufen1-mediated mRNA decay mechanism. Our studies revealed a new stress response mechanism regulated by MAP kinases, in which ADAR1p110 translocates to the cytoplasm and regulates a class of mRNAs required for survival of stressed cells.
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| |
|
| Overall design |
Examination of transcription changes due to ADAR1 and double ADAR1/STAU1 knockdown using RNA-seq
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| |
|
| Contributor(s) |
Nishikura K, Sakurai M |
| Citation(s) |
28436945 |
| Submission date |
Aug 10, 2016 |
| Last update date |
Sep 25, 2019 |
| Contact name |
Priyankara J Wickramasinghe |
| E-mail(s) |
priyaw@wistar.org
|
| Phone |
2154956837
|
| Organization name |
The Wistar Institute
|
| Department |
Bioinformatics
|
| Lab |
Genomics
|
| Street address |
3601 Spruce Street
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (6)
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|
| Relations |
| BioProject |
PRJNA338496 |
| SRA |
SRP081249 |
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