| First Author | Wang J | Year | 2023 |
| Journal | J Genet Genomics | Volume | 50 |
| Issue | 2 | Pages | 87-98 |
| PubMed ID | 35500745 | Mgi Jnum | J:334137 |
| Mgi Id | MGI:7446862 | Doi | 10.1016/j.jgg.2022.04.008 |
| Citation | Wang J, et al. (2023) PRMT5 determines the pattern of polyploidization and prevents liver from cirrhosis and carcinogenesis. J Genet Genomics 50(2):87-98 |
| abstractText | Human hepatocellular carcinoma (HCC) occurs almost exclusively in cirrhotic livers. Here, we report that hepatic loss of protein arginine methyltransferase 5 (PRMT5) in mice is sufficient to cause cirrhosis and HCC in a clinically relevant way. Furthermore, pathological polyploidization induced by hepatic loss of PRMT5 promotes liver cirrhosis and hepatic tumorigenesis in aged liver. The loss of PRMT5 leads to hyper-accumulation of P21 and endoreplication-dependent formation of pathological mono-nuclear polyploid hepatocytes. PRMT5 and symmetric dimethylation at histone H4 arginine 3 (H4R3me2s) directly associate with chromatin of P21 to suppress its transcription. More importantly, loss of P21 rescues the pathological mono-nuclear polyploidy and prevents PRMT5-deficiency-induced liver cirrhosis and HCC. Thus, our results indicate that PRMT5-mediated symmetric dimethylation at histone H4 arginine 3 (H4R3me2s) is crucial for preventing pathological polyploidization, liver cirrhosis and tumorigenesis in mouse liver. |
