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Loss of β-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation
- Source :
- Communications Biology, Vol 3, Iss 1, Pp 1-16 (2020), Communications Biology
- Publication Year :
- 2020
- Publisher :
- Nature Research, 2020.
-
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.<br />Dina Mostafa et al. report that β cell function and identity depends on the deadenylase complex subunit CNOT3. The authors found that Cnot3 was dysregulated in diabetic mice and, when knocked out in wild type, mice have impaired glucose tolerance and gradually develop diabetes.
- Subjects :
- 0301 basic medicine
Male
Proteome
medicine.medical_treatment
Medicine (miscellaneous)
Cell Count
Cell Maturation
RNA decay
Models, Biological
General Biochemistry, Genetics and Molecular Biology
Article
Diabetes Mellitus, Experimental
Impaired glucose tolerance
03 medical and health sciences
0302 clinical medicine
Diabetes mellitus
Insulin-Secreting Cells
Insulin Secretion
medicine
Animals
Insulin
Secretion
Obesity
RNA, Messenger
Progenitor cell
lcsh:QH301-705.5
Mice, Knockout
Messenger RNA
Chemistry
Wild type
Type 2 diabetes
Cell Differentiation
Glucose Tolerance Test
medicine.disease
Lipids
Cell biology
Disease Models, Animal
030104 developmental biology
Glucose
Phenotype
lcsh:Biology (General)
General Agricultural and Biological Sciences
Transcriptome
030217 neurology & neurosurgery
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 23993642
- Volume :
- 3
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Communications Biology
- Accession number :
- edsair.doi.dedup.....9f79eb55baf804216badf666d443ab37