| First Author | Mostafa D | Year | 2020 |
| Journal | Commun Biol | Volume | 3 |
| Issue | 1 | Pages | 476 |
| PubMed ID | 32859966 | Mgi Jnum | J:293814 |
| Mgi Id | MGI:6453761 | Doi | 10.1038/s42003-020-01201-y |
| Citation | Mostafa D, et al. (2020) Loss of beta-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation. Commun Biol 3(1):476 |
| abstractText | Pancreatic beta-cells are responsible for production and secretion of insulin in response to increasing blood glucose levels. Defects in beta-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 beta cell maturation and identity. Mice with beta cell-specific Cnot3 deletion (Cnot3betaKO) exhibit impaired glucose tolerance, decreased beta cell mass, and they gradually develop diabetes. Cnot3betaKO islets display decreased expression of key regulators of beta cell maturation and function. Moreover, they show an increase of progenitor cell markers, beta cell-disallowed genes, and genes relevant to altered beta cell function. Cnot3betaKO 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 beta cell identity. |
