| RRC ID |
60963
|
| Author |
Mostafa D, Yanagiya A, Georgiadou E, Wu Y, Stylianides T, Rutter GA, Suzuki T, Yamamoto T.
|
| Title |
Loss of β-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation.
|
| Journal |
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.
|
| Volume |
3(1)
|
| Pages |
476
|
| Published |
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
|
| Resource |
| Mice |
RBRC09525 |
