title: PRMT5 is essential for the eIF4E-mediated 5'-cap dependent translation.
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 5'-cap dependent translation of HIF-1α. Given that c-Myc and cyclin D1 expressions are also tightly regulated in 5'-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 5'-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 5'-cap dependent translation of proteins essential for proliferation and survival.
authors.affiliation: Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, Chungbuk, Republic of Korea.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Department of Food Bioscience, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, Chungbuk, Republic of Korea.
authors.forename: Yoon-Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, Chungbuk, Republic of Korea.
authors.forename: Gibok
authors.initials: G
authors.lastname: Lee
authors.affiliation: Departments of Pharmacology and Biomedical Science, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Republic of Korea.
authors.forename: Yong-Joon
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, Chungbuk, Republic of Korea.
authors.forename: Beong-Ou
authors.initials: BO
authors.lastname: Lim
authors.affiliation: Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, Chungbuk, Republic of Korea.
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, College of Biomedical & Health Science, Konkuk University, Chungju 380-701, Chungbuk, Republic of Korea.
authors.forename: Dong-Kug
authors.initials: DK
authors.lastname: Choi
authors.affiliation: Departments of Pharmacology and Biomedical Science, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Republic of Korea. Electronic address: parkjw@snu.ac.kr.
authors.forename: Jong-Wan
authors.initials: JW
authors.lastname: Park
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C411571:EIF4ENIF1 protein, human; D029543:Nucleocytoplasmic Transport Proteins; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases
keywords: 5′-Cap dependent translation; Cyclin D1; Protein arginine methyltransferase 5; c-Myc; eIF4E