| First Author | Suzuki T | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 14779 | PubMed ID | 26437789 |
| Mgi Jnum | J:251521 | Mgi Id | MGI:6102457 |
| Doi | 10.1038/srep14779 | Citation | Suzuki T, et al. (2015) CNOT3 suppression promotes necroptosis by stabilizing mRNAs for cell death-inducing proteins. Sci Rep 5:14779 |
| abstractText | The CCR4-NOT complex is conserved in eukaryotes and is involved in mRNA metabolism, though its molecular physiological roles remain to be established. We show here that CNOT3-depleted mouse embryonic fibroblasts (MEFs) undergo cell death. Levels of other complex subunits are decreased in CNOT3-depleted MEFs. The death phenotype is rescued by introduction of wild-type (WT), but not mutated CNOT3, and is not suppressed by the pan-caspase inhibitor, zVAD-fluoromethylketone. Gene expression profiling reveals that mRNAs encoding cell death-related proteins, including receptor-interacting protein kinase 1 (RIPK1) and RIPK3, are stabilized in CNOT3-depleted MEFs. Some of these mRNAs bind to CNOT3, and in the absence of CNOT3 their poly(A) tails are elongated. Inhibition of RIPK1-RIPK3 signaling by a short-hairpin RNA or a necroptosis inhibitor, necrostatin-1, confers viability upon CNOT3-depleted MEFs. Therefore, we conclude that CNOT3 targets specific mRNAs to prevent cells from being disposed to necroptotic death. |
