| First Author | Zhang F | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 3997 |
| PubMed ID | 34183666 | Mgi Jnum | J:340201 |
| Mgi Id | MGI:6725577 | Doi | 10.1038/s41467-021-24302-6 |
| Citation | Zhang F, et al. (2021) The long non-coding RNA betaFaar regulates islet beta-cell function and survival during obesity in mice. Nat Commun 12(1):3997 |
| abstractText | Despite obesity being a predisposing factor for pancreatic beta-cell dysfunction and loss, the mechanisms underlying its negative effect on insulin-secreting cells remain poorly understood. In this study, we identify an islet-enriched long non-coding RNA (lncRNA), which we name beta-cell function and apoptosis regulator (betaFaar). betaFaar is dramatically downregulated in the islets of the obese mice, and a low level of betaFaar is necessary for the development of obesity-associated beta-cell dysfunction and apoptosis. Mechanistically, betaFaar promote the synthesis and secretion of insulin by upregulating islet-specific genes Ins2, NeuroD1, and Creb1 through sponging miR-138-5p. In addition, using quantitative mass spectrometry, we identify TRAF3IP2 and SMURF1 as interacting proteins that are specifically associated with betaFaar. We demonstrate that SMURF1 ubiquitin ligase activity is essential for TRAF3IP2 ubiquitination and activation of NF-kappaB-mediate beta-cell apoptosis. Our experiments provide direct evidence that dysregulated betaFaar contributes to the development of obesity-induced beta-cell injury and apoptosis. |
