ADAR1 controls apoptosis of stressed cells by inhibiting Staufen-mediated mRNA decay
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: Kazuko Nishikura
PROVIDER: MSV000080146 | MassIVE |
SECONDARY ACCESSION(S): PXD004959
REPOSITORIES: MassIVE
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Project description: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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