論文 - 詳細
| RRC ID | 80900 |
|---|---|
| 著者 | Tsai YT, Chang CH, Tsai HY. |
| タイトル | Rege-1 promotes C. elegans survival by modulating IIS and TOR pathways. |
| ジャーナル | PLoS Genet |
| Abstract |
Metabolic pathways are known to sense the environmental stimuli and result in physiological adjustments. The responding processes need to be tightly controlled. Here, we show that upon encountering P. aeruginosa, C. elegans upregulate the transcription factor ets-4, but this upregulation is attenuated by the ribonuclease, rege-1. As such, mutants with defective REGE-1 ribonuclease activity undergo ets-4-dependent early death upon challenge with P. aeruginosa. Furthermore, mRNA-seq analysis revealed associated global changes in two key metabolic pathways, the IIS (insulin/IGF signaling) and TOR (target of rapamycin) kinase signaling pathways. In particular, failure to degrade ets-4 mRNA in activity-defective rege-1 mutants resulted in upregulation of class II longevity genes, which are suppressed during longevity, and activation of TORC1 kinase signaling pathway. Genetic inhibition of either pathway way was sufficient to abolish the poor survival phenotype in rege-1 worms. Further analysis of ETS-4 ChIP data from ENCODE and characterization of one upregulated class II gene, ins-7, support that the Class II genes are activated by ETS-4. Interestingly, deleting an upregulated Class II gene, acox-1.5, a peroxisome β-oxidation enzyme, largely rescues the fat lost phenotype and survival difference between rege-1 mutants and wild-types. Thus, rege-1 appears to be crucial for animal survival due to its tight regulation of physiological responses to environmental stimuli. This function is reminiscent of its mammalian ortholog, Regnase-1, which modulates the intestinal mTORC1 signaling pathway. |
| 巻・号 | 19(8) |
| ページ | e1010869 |
| 公開日 | 2023-8-1 |
| DOI | 10.1371/journal.pgen.1010869 |
| PII | PGENETICS-D-22-01364 |
| PMID | 37556491 |
| PMC | PMC10441803 |
| MeSH | Animals Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Insulin / genetics Insulin / metabolism Mammals / genetics RNA, Messenger / metabolism Ribonucleases / genetics Ribonucleases / metabolism Signal Transduction / genetics |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1714 tm15936 tm2265 tm2001 tm8184 |