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Title: PRMT5 is essential for the eIF4E-mediated 5′-cap dependent translation

Highlights: • PRMT5 participates in syntheses of HIF-1α, c-Myc and cyclin D1 proteins. • PRMT5 promotes the 5′-cap dependent translation. • PRMT5 is required for eIF4E binding to mRNA 5′-cap. • PRMT5 is essential for eIF4E-dependent cell proliferation. - 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-deficeintmore » 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.« less
Authors:
 [1] ;  [2] ;  [1] ;  [3] ; ;  [1] ;  [4] ;  [3]
  1. Department of Biomedical Chemistry, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Chungbuk (Korea, Republic of)
  2. Department of Food Bioscience, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Chungbuk (Korea, Republic of)
  3. Departments of Pharmacology and Biomedical Science, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799 (Korea, Republic of)
  4. Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Chungbuk (Korea, Republic of)
Publication Date:
OSTI Identifier:
22416772
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 452; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANOXIA; ARGININE; CELL CYCLE; CELL PROLIFERATION; MESSENGER-RNA; METHYL TRANSFERASES; STRESSES; SYNTHESIS