| First Author | Xiong L | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 1 | Pages | 108680 |
| PubMed ID | 38226164 | Mgi Jnum | J:344463 |
| Mgi Id | MGI:7575382 | Doi | 10.1016/j.isci.2023.108680 |
| Citation | Xiong L, et al. (2024) circGlis3 promotes beta-cell dysfunction by binding to heterogeneous nuclear ribonucleoprotein F and encoding Glis3-348aa protein. iScience 27(1):108680 |
| abstractText | Circular RNAs (circRNAs) are crucial regulators of beta-cell function and are involved in lipotoxicity-induced beta-cell damage in type 2 diabetes mellitus (T2DM). We previously identified that circGlis3, a circRNA derived from exon 4 of the diabetes susceptibility gene Glis3, was upregulated in lipotoxic beta cells. However, the functional role and molecular mechanism of circGlis3 in beta cells remain largely unknown. Here, we revealed that the splicing factor CUGBP Elav-Like Family Member 1 (CELF1) facilitated the biogenesis of circGlis3. Moreover, we established a transgenic mouse model and confirmed that the overexpression of circGlis3 impaired beta-cell function. Mechanistically, circGlis3 bound to heterogeneous nuclear ribonucleoprotein F (hnRNPF) and blocked its nuclear translocation, thereby reducing Sirt1 levels. Additionally, circGlis3 encoded a 348aa protein that interacted with GLIS3 and inhibited its transcriptional activity. Our data uncover a critical role of circGlis3 in beta-cell dysfunction, suggesting that circGlis3 may be a potential therapeutic target for T2DM. |
