| First Author | Elizalde M | Year | 2014 |
| Journal | J Clin Invest | Volume | 124 |
| Issue | 7 | Pages | 2909-20 |
| PubMed ID | 24865429 | Mgi Jnum | J:213277 |
| Mgi Id | MGI:5584041 | Doi | 10.1172/JCI74382 |
| Citation | Elizalde M, et al. (2014) Splicing regulator SLU7 is essential for maintaining liver homeostasis. J Clin Invest 124(7):2909-20 |
| abstractText | A precise equilibrium between cellular differentiation and proliferation is fundamental for tissue homeostasis. Maintaining this balance is particularly important for the liver, a highly differentiated organ with systemic metabolic functions that is endowed with unparalleled regenerative potential. Carcinogenesis in the liver develops as the result of hepatocellular de-differentiation and uncontrolled proliferation. Here, we identified SLU7, which encodes a pre-mRNA splicing regulator that is inhibited in hepatocarcinoma, as a pivotal gene for hepatocellular homeostasis. SLU7 knockdown in human liver cells and mouse liver resulted in profound changes in pre-mRNA splicing and gene expression, leading to impaired glucose and lipid metabolism, refractoriness to key metabolic hormones, and reversion to a fetal-like gene expression pattern. Additionally, loss of SLU7 also increased hepatocellular proliferation and induced a switch to a tumor-like glycolytic phenotype. Slu7 governed the splicing and/or expression of multiple genes essential for hepatocellular differentiation, including serine/arginine-rich splicing factor 3 (Srsf3) and hepatocyte nuclear factor 4alpha (Hnf4alpha), and was critical for cAMP-regulated gene transcription. Together, out data indicate that SLU7 is central regulator of hepatocyte identity and quiescence. |
