| First Author | Xie X | Year | 2024 |
| Journal | Adv Sci (Weinh) | Volume | 11 |
| Issue | 42 | Pages | e2407774 |
| PubMed ID | 39297407 | Mgi Jnum | J:361035 |
| Mgi Id | MGI:7855453 | Doi | 10.1002/advs.202407774 |
| Citation | Xie X, et al. (2024) PARN Maintains RNA Stability to Regulate Insulin Maturation and GSIS in Pancreatic beta Cells. Adv Sci (Weinh) 11(42):e2407774 |
| abstractText | Diabetes, a metabolic disorder characterized by hyperglycemia, underscores the importance of normal pancreatic beta-cell development and function in maintaining glucose homeostasis. Poly(A)-specific ribonuclease (PARN) serves as the principal regulator of messenger RNA (mRNA) stability, yet its specific role in pancreatic beta cells remains unclear. This study utilizes mice with targeted PARN deficiency in beta cells to elucidate this role. Notably, Parn conditional knockout mice present unaltered beta-cell development and insulin sensitivity but reduced glucose-stimulated insulin secretion (GSIS). The observed outcomes are corroborated in NIT-1 cells. Furthermore, transcriptomic analyses reveal aberrant mRNA expression of genes crucial for insulin secretion in PARN-deficient beta cells. Insights from linear amplification of complementary DNA ends and sequencing and coimmunoprecipitation experiments reveal an interaction between PARN and polypyrimidine tract-binding protein 1 (PTBP1), regulating the RNA stability of solute carrier family 30, member 8 (Slc30a8) and carbohydrate sulfotransferase 3 (Chst3). Interference with either PARN or PTBP1 disrupts this stability. These data indicate that PARN deficiency hampers GSIS and insulin maturation by destabilizing Slc30a8 and Chst3 RNAs. These findings provide compelling evidence indicating that PARN is a potential therapeutic target for enhancing insulin maturation and secretion. |
