Dissecting the functional role of RPL19 in translational regulation

  • 劉 建甫

Student thesis: Master's Thesis


The ribosome is a complex composed of rRNAs and ribosomal proteins Traditionally ribosome can translate proteins and ribosomal proteins were considered as co-factors to execute the protein translation But in the last decade numerous studies have demonstrated that ribosomal proteins not only play a role as co-factors of translation complex but also regulate the protein synthesis of specific mRNAs However the mechanism of these ribosomal proteins to regulate the protein synthesis is still unclear Cyclin D1 plays an important role in cell cycle progression The synthesis of cyclin D1 is initiated during G1 phase and drives the G1/S phase transition From the previous study the ribosomal protein L19(RPL19) was reported to regulate the cyclin D1 protein expression It indicated RPL19 may be a regulator of cell cycle through controlling cyclin D1 protein expression And then we identified that RPL19 can cooperate with heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) to regulate cell cycle progression through regulating the internal ribosome entry site (IRES) activity of cyclin D1 Furthermore we confirmed that silencing RPL19 expression would reduce cyclin D1 translation efficiency and block the cell cycle in G1 phase Besides we are also interested in that if there are other cell cycle process genes being regulated by RPL19 Cyclin E1 has been considered an essential and master regulator of progression through G1 phase of the cell cycle We find that the 5’UTR of cyclin E1 mRNA carries an IRES element and RPL19 plays a role in regulating the IRES activity and translation efficiency of cyclin E1 We also see that RPL19 has interaction with cyclin E1 mRNA at G1 phase To better understand the role of RPL19 in cell process we analyzed ribosomal profiling of knock-down RPL19 and found that RPL19 main impact cell-cycle and apoptosis progress Mitogen-activated protein kinase 1(MAPK1) have a positive role in controlling normal and Ras-dependent cell proliferation Furthermore we identified MAPK1 is regulated by RPL19 through IRES activity and translation efficiency We think that RPL19 may be a model to explain the mechanism of the ribosomal proteins to regulate the specific protein synthesis To sum up we identified that RPL19 regulates cyclin D1 cyclin E1 and MAPK1’s protein expression through regulating their IRES activities and translation efficiency Through these mechanisms RPL19 can mainly regulate cell cycle and apoptosis process
Date of Award2015 Aug 25
Original languageEnglish
SupervisorTa-Chien Tseng (Supervisor)

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