核醣體蛋白是由許多核醣體次單元所組成(分成大次單元:RPL家族和小次單元:RPS家族)，主要參與在細胞轉譯作用的過程中。大腸桿菌等等的細菌和古細菌是擁有30S小次單元和50S大次單元的生物，而人類以及酵母菌則是擁有40S小次單元和60S大次單元的生物。在哺乳動物中，核醣體蛋白大約含有2000基因序列，但大部分的序列被預測偽基因，且有功能的核醣體蛋白幾乎只以單基因組成。此外，核醣體RNA (rRNA) 的多樣性以及核醣體相關調控因子的活性可促使產生出“專一性的核醣體”並實際地影響基因體的模板轉譯成有功能的蛋白質。核醣體蛋白RPL19是一種在人體中由RPL19基因轉譯成的蛋白質，也是組成核醣體大次單元(60S)的一員。在除了SW620之外的大腸直腸癌中，RPL19會透過cyclin D1的IRES
活性來影響轉譯效率，還會和hnRNP A1共同來跟cyclin D1 mRNA進行交互作用。另外，先前的研究也證明了在HeLa細胞中RPL19可調控CTGF的轉譯效率，所以我們便在SW480中證明了CTGF能以IRES 調控的機轉來啟動轉譯的起始，還發現當抑制RPL19時，CTGF的IRES活性會有下調的情況出現。除此之外，我們的實驗更以RNA免疫沉澱法驗證了RPL19可和hnRNP A1合作來調節CTGFmRNA。在那之後，我們先降低hnRNP A1的表現量，再以西方點墨法和報導基因檢測法分別來偵測並證實cyclin D1和CTGF的蛋白質表現量和IRES活性有受到hnRNP A1影響。接著我們也以蛋白質免疫沉澱法來分析hnRNP A1是否會與RPL19結合在一起，而其結果是肯定的。總結來說，我們的研究驗證了hnRNP A1 與RPL19會在SW480中一起結合在cyclin D1和CTGFmRNA上來控制轉譯作用，而當cap依賴型的轉譯起始作用因細胞外在壓力環境而受到影響時，細胞還可以選擇透過IRES的區域來啟動蛋白質的合成。

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.

Balasubramanian, S., D. Zheng, Y. J. Liu, G. Fang, A. Frankish, N. Carriero, R. Robilotto, P. Cayting and M. Gerstein (2009). "Comparative analysis of processed ribosomal protein pseudogenes in four mammalian genomes." Genome Biol 10(1): R2.
Bartkova, J., J. Lukas, H. Muller, M. Strauss, B. Gusterson and J. Bartek (1995). "Abnormal patterns of D-type cyclin expression and G1 regulation in human head and neck cancer." Cancer Res 55(4): 949-956.
Bee, A., Y. Ke, S. Forootan, K. Lin, C. Beesley, S. E. Forrest and C. S. Foster (2006). "Ribosomal protein l19 is a prognostic marker for human prostate cancer." Clin Cancer Res 12(7 Pt 1): 2061-2065.
Benvenuto, M., P. Sileri, P. Rossi, L. Masuelli, M. Fantini, M. Nanni, L. Franceschilli, G. Sconocchia, G. Lanzilli, R. Arriga, G. Faggioni, F. Lista, A. Orlandi, V. Manzari, A. L. Gaspari, A. Modesti and R. Bei (2015). "Natural humoral immune response to ribosomal P0 protein in colorectal cancer patients." J Transl Med 13: 101.
Bert, A. G., R. Grepin, M. A. Vadas and G. J. Goodall (2006). "Assessing IRES activity in the HIF-1alpha and other cellular 5' UTRs." Rna 12(6): 1074-1083.
Bonnal, S., C. Schaeffer, L. Creancier, S. Clamens, H. Moine, A. C. Prats and S. Vagner (2003). "A single internal ribosome entry site containing a G quartet RNA structure drives fibroblast growth factor 2 gene expression at four alternative translation initiation codons." J Biol Chem 278(41): 39330-39336.
Cornelis, S., Y. Bruynooghe, G. Denecker, S. Van Huffel, S. Tinton and R. Beyaert (2000). "Identification and characterization of a novel cell cycle-regulated internal ribosome entry site." Mol Cell 5(4): 597-605.
Crick, F. H. (1968). "The origin of the genetic code." J Mol Biol 38(3): 367-379.
Draptchinskaia, N., P. Gustavsson, B. Andersson, M. Pettersson, T. N. Willig, I. Dianzani, S. Ball, G. Tchernia, J. Klar, H. Matsson, D. Tentler, N. Mohandas, B. Carlsson and N. Dahl (1999). "The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia." Nat Genet 21(2): 169-175.
Dressman, M. A., A. Baras, R. Malinowski, L. B. Alvis, I. Kwon, T. M. Walz and M. H. Polymeropoulos (2003). "Gene expression profiling detects gene amplification and differentiates tumor types in breast cancer." Cancer Res 63(9): 2194-2199.
Dreyfuss, G., V. N. Kim and N. Kataoka (2002). "Messenger-RNA-binding proteins and the messages they carry." Nat Rev Mol Cell Biol 3(3): 195-205.
Ebert, B. L. (2009). "Deletion 5q in myelodysplastic syndrome: a paradigm for the study of hemizygous deletions in cancer." Leukemia 23(7): 1252-1256.
Evans, J. R., S. A. Mitchell, K. A. Spriggs, J. Ostrowski, K. Bomsztyk, D. Ostarek and A. E. Willis (2003). "Members of the poly (rC) binding protein family stimulate the activity of the c-myc internal ribosome entry segment in vitro and in vivo." Oncogene 22(39): 8012-8020.
Fantl, V., G. Stamp, A. Andrews, I. Rosewell and C. Dickson (1995). "Mice lacking cyclin D1 are small and show defects in eye and mammary gland development." Genes Dev 9(19): 2364-2372.
Faye, M. D. and M. Holcik (2015). "The role of IRES trans-acting factors in carcinogenesis." Biochim Biophys Acta 1849(7): 887-897.
Feng, B., T. T. Dong, L. L. Wang, H. M. Zhou, H. C. Zhao, F. Dong and M. H. Zheng (2012). "Colorectal cancer migration and invasion initiated by microRNA-106a." PLoS One 7(8): e43452.
Fernandez, J., I. Yaman, R. Mishra, W. C. Merrick, M. D. Snider, W. H. Lamers and M. Hatzoglou (2001). "Internal ribosome entry site-mediated translation of a mammalian mRNA is regulated by amino acid availability." J Biol Chem 276(15): 12285-12291.
Gebauer, F. and M. W. Hentze (2004). "Molecular mechanisms of translational control." Nat Rev Mol Cell Biol 5(10): 827-835.
Hewitt, R. E., A. McMarlin, D. Kleiner, R. Wersto, P. Martin, M. Tsokos, G. W. Stamp and W. G. Stetler-Stevenson (2000). "Validation of a model of colon cancer progression." J Pathol 192(4): 446-454.
Huang, C. J., C. C. Chien, S. H. Yang, C. C. Chang, H. L. Sun, Y. C. Cheng, C. C. Liu, S. C. Lin and C. M. Lin (2008). "Faecal ribosomal protein L19 is a genetic prognostic factor for survival in colorectal cancer." J Cell Mol Med 12(5b): 1936-1943.
Huang, C. J., S. H. Yang, C. L. Lee, Y. C. Cheng, S. Y. Tai and C. C. Chien (2013). "Ribosomal protein S27-like in colorectal cancer: a candidate for predicting prognoses." PLoS One 8(6): e67043.
Jackson, R. J., C. U. Hellen and T. V. Pestova (2010). "The mechanism of eukaryotic translation initiation and principles of its regulation." Nat Rev Mol Cell Biol 11(2): 113-127.
Jang, S. K., M. V. Davies, R. J. Kaufman and E. Wimmer (1989). "Initiation of protein synthesis by internal entry of ribosomes into the 5' nontranslated region of encephalomyocarditis virus RNA in vivo." J Virol 63(4): 1651-1660.
Jang, S. K., H. G. Krausslich, M. J. Nicklin, G. M. Duke, A. C. Palmenberg and E. Wimmer (1988). "A segment of the 5' nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation." J Virol 62(8): 2636-2643.
Jares, P., D. Colomer and E. Campo (2007). "Genetic and molecular pathogenesis of mantle cell lymphoma: perspectives for new targeted therapeutics." Nat Rev Cancer 7(10): 750-762.
Jiao, J., L. Huang, F. Ye, M. Shi, X. Cheng, X. Wang, D. Hu, X. Xie and W. Lu (2013). "Cyclin D1 affects epithelial-mesenchymal transition in epithelial ovarian cancer stem cell-like cells." Onco Targets Ther 6: 667-677.
Jin, M., S. Inoue, T. Umemura, J. Moriya, M. Arakawa, K. Nagashima and H. Kato (2001). "Cyclin D1, p16 and retinoblastoma gene product expression as a predictor for prognosis in non-small cell lung cancer at stages I and II." Lung Cancer 34(2): 207-218.
Jo, O. D., J. Martin, A. Bernath, J. Masri, A. Lichtenstein and J. Gera (2008). "Heterogeneous nuclear ribonucleoprotein A1 regulates cyclin D1 and c-myc internal ribosome entry site function through Akt signaling." J Biol Chem 283(34): 23274-23287.
Kondrashov, N., A. Pusic, C. R. Stumpf, K. Shimizu, A. C. Hsieh, S. Xue, J. Ishijima, T. Shiroishi and M. Barna (2011). "Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning." Cell 145(3): 383-397.
Kuroda, K., M. Takenoyama, T. Baba, Y. Shigematsu, H. Shiota, Y. Ichiki, M. Yasuda, H. Uramoto, T. Hanagiri and K. Yasumoto (2010). "Identification of ribosomal protein L19 as a novel tumor antigen recognized by autologous cytotoxic T lymphocytes in lung adenocarcinoma." Cancer Sci 101(1): 46-53.
Liang, F., J. Liang, W. Q. Wang, J. P. Sun, E. Udho and Z. Y. Zhang (2007). "PRL3 promotes cell invasion and proliferation by down-regulation of Csk leading to Src activation." J Biol Chem 282(8): 5413-5419.
Macejak, D. G. and P. Sarnow (1991). "Internal initiation of translation mediated by the 5' leader of a cellular mRNA." Nature 353(6339): 90-94.
Martin, I., J. W. Kim, B. D. Lee, H. C. Kang, J. C. Xu, H. Jia, J. Stankowski, M. S. Kim, J. Zhong, M. Kumar, S. A. Andrabi, Y. Xiong, D. W. Dickson, Z. K. Wszolek, A. Pandey, T. M. Dawson and V. L. Dawson (2014). "Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease." Cell 157(2): 472-485.
Mokrejs, M., V. Vopalensky, O. Kolenaty, T. Masek, Z. Feketova, P. Sekyrova, B. Skaloudova, V. Kriz and M. Pospisek (2006). "IRESite: the database of experimentally verified IRES structures (www.iresite.org)." Nucleic Acids Res 34(Database issue): D125-130.
Moller, P., K. Koretz, F. Leithauser, S. Bruderlein, C. Henne, A. Quentmeier and P. H. Krammer (1994). "Expression of APO-1 (CD95), a member of the NGF/TNF receptor superfamily, in normal and neoplastic colon epithelium." Int J Cancer 57(3): 371-377.
Moran-Jones, K., B. S. Gloss, R. Murali, D. K. Chang, E. K. Colvin, M. D. Jones, S. Yuen, V. M. Howell, L. M. Brown, C. W. Wong, S. M. Spong, C. J. Scarlett, N. F. Hacker, S. Ghosh, S. C. Mok, M. J. Birrer and G. Samimi (2015). "Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer." Oncotarget 6(42): 44551-44562.
Morrish, B. C. and M. G. Rumsby (2002). "The 5' untranslated region of protein kinase Cdelta directs translation by an internal ribosome entry segment that is most active in densely growing cells and during apoptosis." Mol Cell Biol 22(17): 6089-6099.
Narla, A. and B. L. Ebert (2010). "Ribosomopathies: human disorders of ribosome dysfunction." Blood 115(16): 3196-3205.
Nieminen, T. T., M. F. O'Donohue, Y. Wu, H. Lohi, S. W. Scherer, A. D. Paterson, P. Ellonen, W. M. Abdel-Rahman, S. Valo, J. P. Mecklin, H. J. Jarvinen, P. E. Gleizes and P. Peltomaki (2014). "Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency." Gastroenterology 147(3): 595-598.e595.
Parenteau, J., M. Durand, G. Morin, J. Gagnon, J. F. Lucier, R. J. Wellinger, B. Chabot and S. A. Elela (2011). "Introns within ribosomal protein genes regulate the production and function of yeast ribosomes." Cell 147(2): 320-331.
Pelletier, J. and N. Sonenberg (1988). "Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA." Nature 334(6180): 320-325.
Pogue-Geile, K., J. R. Geiser, M. Shu, C. Miller, I. G. Wool, A. I. Meisler and J. M. Pipas (1991). "Ribosomal protein genes are overexpressed in colorectal cancer: isolation of a cDNA clone encoding the human S3 ribosomal protein." Mol Cell Biol 11(8): 3842-3849.
Pyronnet, S., L. Pradayrol and N. Sonenberg (2000). "A cell cycle-dependent internal ribosome entry site." Mol Cell 5(4): 607-616.
Satyanarayana, A. and P. Kaldis (2009). "Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms." Oncogene 28(33): 2925-2939.
Sewify, E. M., O. A. Afifi, E. Mosad, A. H. Zaki and S. A. El Gammal (2014). "Cyclin D1 amplification in multiple myeloma is associated with multidrug resistance expression." Clin Lymphoma Myeloma Leuk 14(3): 215-222.
Shamma, A., Y. Doki, H. Shiozaki, T. Tsujinaka, M. Yamamoto, M. Inoue, M. Yano and M. Monden (2000). "Cyclin D1 overexpression in esophageal dysplasia: a possible biomarker for carcinogenesis of esophageal squamous cell carcinoma." Int J Oncol 16(2): 261-266.
Sherr, C. J. (1993). "Mammalian G1 cyclins." Cell 73(6): 1059-1065.
Spriggs, K. A., M. Stoneley, M. Bushell and A. E. Willis (2008). "Re-programming of translation following cell stress allows IRES-mediated translation to predominate." Biol Cell 100(1): 27-38.
Stoneley, M., S. A. Chappell, C. L. Jopling, M. Dickens, M. MacFarlane and A. E. Willis (2000). "c-Myc protein synthesis is initiated from the internal ribosome entry segment during apoptosis." Mol Cell Biol 20(4): 1162-1169.
Twigg, S. M., Z. Cao, M. C. SV, W. C. Burns, G. Brammar, J. M. Forbes and M. E. Cooper (2002). "Renal connective tissue growth factor induction in experimental diabetes is prevented by aminoguanidine." Endocrinology 143(12): 4907-4915.
Wool, I. G. (1996). "Extraribosomal functions of ribosomal proteins." Trends Biochem Sci 21(5): 164-165.
Xue, S. and M. Barna (2012). "Specialized ribosomes: a new frontier in gene regulation and organismal biology." Nat Rev Mol Cell Biol 13(6): 355-369.
Yokoi, H., M. Mukoyama, A. Sugawara, K. Mori, T. Nagae, H. Makino, T. Suganami, K. Yahata, Y. Fujinaga, I. Tanaka and K. Nakao (2002). "Role of connective tissue growth factor in fibronectin expression and tubulointerstitial fibrosis." Am J Physiol Renal Physiol 282(5): F933-942.
Zhu, X., J. Zhong, Z. Zhao, J. Sheng, J. Wang, J. Liu, K. Cui, J. Chang, H. Zhao and S. Wong (2015). "Epithelial derived CTGF promotes breast tumor progression via inducing EMT and collagen I fibers deposition." Oncotarget 6(28): 25320-25338.