Reference - Detail
| RRC ID | 45524 |
|---|---|
| Author | Suzuki T, Kikuguchi C, Sharma S, Sasaki T, Tokumasu M, Adachi S, Natsume T, Kanegae Y, Yamamoto T. |
| Title | CNOT3 suppression promotes necroptosis by stabilizing mRNAs for cell death-inducing proteins. |
| Journal | Sci Rep |
| Abstract |
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. |
| Volume | 5 |
| Pages | 14779 |
| Published | 2015-10-6 |
| DOI | 10.1038/srep14779 |
| PII | srep14779 |
| PMID | 26437789 |
| PMC | PMC4594005 |
| MeSH | Amino Acid Chloromethyl Ketones / pharmacology Animals Caspase Inhibitors / pharmacology Cell Death / drug effects Cell Survival / drug effects Cysteine Proteinase Inhibitors / pharmacology Embryo, Mammalian Fibroblasts / cytology Fibroblasts / drug effects Fibroblasts / metabolism* Gene Expression Regulation Imidazoles / pharmacology Indoles / pharmacology Leupeptins / pharmacology Mice Primary Cell Culture Protein Binding RNA Stability RNA, Messenger / genetics* RNA, Messenger / metabolism RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Receptor-Interacting Protein Serine-Threonine Kinases / antagonists & inhibitors Receptor-Interacting Protein Serine-Threonine Kinases / genetics* Receptor-Interacting Protein Serine-Threonine Kinases / metabolism Signal Transduction Transcription Factors / genetics* Transcription Factors / metabolism |
| IF | 3.998 |
| Times Cited | 18 |
| WOS Category | CELL BIOLOGY |
| Resource | |
| DNA material | pMXs-Puro-Flag-mouse CNOT3 full length (RDB14289) pMXs-Puro-Flag-mouseCNOT3 (1-606) (RDB14290) pMXs-Puro-Flag-mouse CNOT3 (245-end) (RDB14291). |