Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10754384 | Biochemical and Biophysical Research Communications | 2014 | 6 Pages |
Abstract
It is becoming clear that PRMT5 plays essential roles in cell cycle progression, survival, and responses to external stresses. However, the precise mechanisms underlying such roles of PRMT5 have not been clearly understood. Previously, we have demonstrated that PRMT5 participates in cellular adaptation to hypoxia by ensuring 5â²-cap dependent translation of HIF-1α. Given that c-Myc and cyclin D1 expressions are also tightly regulated in 5â²-cap dependent manner, we here tested the possibility that PRMT5 promotes cell proliferation by increasing de novo syntheses of the oncoproteins. c-Myc and cyclin D1 were found to be noticeably downregulated by PRMT5 knock-down. A RNA immunoprecipitation analysis, which can identify RNA-protein interactions, showed that PRMT5 is required for the interaction among eIF4E and 5â²-UTRs of HIF-1α, c-Myc and cyclin D1 mRNAs. In addition, PRMT5 knock-down inhibited cell proliferation by inducing cell cycle arrest at the G1 phase. More importantly, ectopic expression of eIF4E significantly rescued the cell cycle progression and cell proliferation even in PRMT5-deficeint condition. Based on these results, we propose that PRMT5 determines cell fate by regulating 5â²-cap dependent translation of proteins essential for proliferation and survival.
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Authors
Ji-Hong Lim, Yoon-Mi Lee, Gibok Lee, Yong-Joon Choi, Beong-Ou Lim, Young Jun Kim, Dong-Kug Choi, Jong-Wan Park,