論文 - 詳細
| RRC ID | 60963 |
|---|---|
| 著者 | Mostafa D, Yanagiya A, Georgiadou E, Wu Y, Stylianides T, Rutter GA, Suzuki T, Yamamoto T. |
| タイトル | Loss of β-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation. |
| ジャーナル | Commun Biol |
| Abstract |
Pancreatic β-cells are responsible for production and secretion of insulin in response to increasing blood glucose levels. Defects in β-cell function lead to hyperglycemia and diabetes mellitus. Here, we show that CNOT3, a CCR4-NOT deadenylase complex subunit, is dysregulated in islets in diabetic db/db mice, and that it is essential for murine β cell maturation and identity. Mice with β cell-specific Cnot3 deletion (Cnot3βKO) exhibit impaired glucose tolerance, decreased β cell mass, and they gradually develop diabetes. Cnot3βKO islets display decreased expression of key regulators of β cell maturation and function. Moreover, they show an increase of progenitor cell markers, β cell-disallowed genes, and genes relevant to altered β cell function. Cnot3βKO islets exhibit altered deadenylation and increased mRNA stability, partly accounting for the increased expression of those genes. Together, these data reveal that CNOT3-mediated mRNA deadenylation and decay constitute previously unsuspected post-transcriptional mechanisms essential for β cell identity. |
| 巻・号 | 3(1) |
| ページ | 476 |
| 公開日 | 2020-8-28 |
| DOI | 10.1038/s42003-020-01201-y |
| PII | 10.1038/s42003-020-01201-y |
| PMID | 32859966 |
| PMC | PMC7455721 |
| MeSH | Animals Cell Count Cell Differentiation / genetics Diabetes Mellitus, Experimental / genetics Diabetes Mellitus, Experimental / pathology* Disease Models, Animal Glucose / toxicity Glucose Tolerance Test Insulin / metabolism Insulin Secretion Insulin-Secreting Cells / metabolism Insulin-Secreting Cells / pathology* Lipids / toxicity Male Mice, Knockout Models, Biological Obesity / pathology Phenotype Proteome / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Transcription Factors / metabolism* Transcriptome / genetics |
| IF | 4.165 |
| 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 | 31 |
| 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 | |
| 実験動物マウス | RBRC09525 |