PLX251440

GSE85455: ADAR1 controls apoptosis of stressed cells by inhibiting Staufen-mediated mRNA decay

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

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 3UTR dsRNA structures such as those consisting of inverted Alu repeats. ADAR1p110 competitively inhibits binding of Staufen1 to the 3UTR 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. SOURCE: Priyankara,J,Wickramasinghe (priyaw@wistar.org) - Lieberman The Wistar Institute