To study the functional role of translational regulation for RPL19 in colorectal cancer

摘要

Ribosomal proteins are composed of the ribosomal subunits (large subunit: RPL family; small subunit: RPS family) and involve in the cellular process of translation E coli other bacteria and Archaea have a 30S small subunit and a 50S large subunit whereas humans and yeasts have a 40S small subunit and a 60S large subunit In mammals there are approximately 2 000 sequences encoding ribosomal proteins but most of them are predicted to be pseudogenes and most functional ribosomal proteins are encoded by a single gene Furthermore the diversity of ribosomal RNA (rRNA) and the activity of ribosome-associated factors may generate ‘specialized ribosomes’ that have a substantial impact on how the genomic template is translated into functional proteins Ribosomal protein L19 a protein that in humans is encoded by the RPL19 gene which is a component of the ribosome large subunit (60S) RPL19 proteins affected the translational efficiency by IRES activity of cyclin D1 and bound with hnRNP A1 proteins to interact with cyclin D1 mRNA in colorectal cancer cells except SW620 cells Moreover previous study also identified that RPL19 proteins regulated the translational efficiency of CTGF in HeLa cells We have proved that CTGF mRNA were translated by IRES-mediated mechanism and found IRES activity of CTGF was down-regulated by knockdown RPL19 in SW480 cells Besides we identified that RPL19 and hnRNP A1 proteins both interact with CTGF mRNA by RNA Immunoprecipitation assay After then we analyzed the protein expression of cyclin D1 and CTGF by western blotting and confirmed that RPL19 proteins mediated cyclin D1 and CTGF through controlling IRES-dependent translation in SW480 cells by reporter assay while knocking-down the expression level of hnRNP A1 In conclusion we demonstrated hnRNP A1 and RPL19 proteins bound together to recruit cyclin D1 and CTGF mRNA and started the protein synthesis by IRES element in SW480 cells

獎項日期	2016 8月 2
原文	English
監督員	Ta-Chien Tseng (Supervisor)