Extra-Ribosomal Functions of the Ribosomal Protein, RPS3 as Predicted by In Silico Analysis

Authors

  • Edmund Ui-Hang Sim
  • Chin-Ming Er

DOI:

https://doi.org/10.33736/bjrst.236.2014

Keywords:

Protein models, RPS3, structural neighbours

Abstract

Products of ribosomal protein (RP) genes have been found to play extra-ribosomal roles that range from DNA repair to RNA splicing. Their association with congenital disorders or cancers has also been widely documented. However, the relatively large number of different RPs, each with perhaps unique biological roles, has compounded the comprehensive elucidation of the physiological functions of each RPs. Experimental functional studies on the many and variegated RPs are labour intensive, time-consuming and costly. Moreover, experimental studies unguided by theoretically insights entail inaccurate results. Therefore, knowledge on the actual roles of these proteins remains largely undefined. A valid alternative is the use of bioinformatics resources to computationally predict functional roles of these biomolecules. Findings from such in silico studies of the RPS3 are reported herein. We reveal an array of possible extra-ribosomal functions that includes regulation of transcription (including via NF-κB-mediated, POK-induced and DNA-dependent), regulation of p53 activities and its stabilisation, inflammatory immune response, modulation of nNOS activities, and anti-oxidative capabilities. Our findings provide computational prediction of de novo extra-ribosomal functions of RPS3. These results will enhance the theoretical basis for designing future experimental studies on elucidating its definitive physiological roles.

References

Ahn, E.H., Kim, D.W., Kang, H.W., Shin, M.J., Won, M.H., Kim, J., Kim, D.J., Kwon, O.S., Kang, T.C., Han, K.H., Park, J., Eum, W.S., & Choi, S.Y. (2010). Transduced PEP-1-ribosomal protein S3 (rpS3) ameliorates 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice. Toxicology, 276: 192-197.

https://doi.org/10.1016/j.tox.2010.08.004

Bassoe, C.F., Bruserud, O., Pryme, I.F., & Vedeler, A. (1998). Ribosomal proteins sustain morphology, function and phenotype in acute myeloid leukemia blasts. Leukemia Research, 22: 329-339.

https://doi.org/10.1016/S0145-2126(97)00178-1

Bates, P.A., Kelley, L.A., MacCallum, R.M., & Sternberg, M.J.E. (2001). Enhancement of protein modelling by human intervention in applying the automatic programs 3D-JIGSAW and 3D-PSSM. Proteins, Suppl. 5: 39-46.

https://doi.org/10.1002/prot.1168

Cahlin, C., Gelin, J., Delbro, D., Lönnrot, C., Doi, C., & Lundholm, K. (2000). Effect of cyclooxygenase and nitric oxide synthase inhibitors on tumor growth in mouse tumor models with and without cancer cachexia related to prostanoids. Cancer Research, 60: 1742-1749.

Chan, S.L.L. & Sim, E.U.H. (2013). Bioinformatics analysis of the ribosomal proteins, RPL27, RPL37a and RPL41: 3-D protein modeling and protein-protein interaction prediction. International Journal of Bioscience, Biochemistry and Bioinformatics, 3: 10-15.

https://doi.org/10.7763/IJBBB.2013.V3.154

Cheng, Q., Lau, W.M., Chew, S.H., Ho, T.H., Tay, S.K., & Hui, K.M. (2002). Identification of molecular markers for the early detection of human squamous cell carcinoma of the uterine cervix. British Journal of Cancer, 86: 274-281.

https://doi.org/10.1038/sj.bjc.6600038

Choi, S.H., Kim, S.Y., An, J.J., Lee, S.H., Kim, D.W., Won, M.H., Kang, T.C., Park, J., Eum, W.S., Kim, J., & Choi, S.Y. (2006). Immunohistochemical studies of human ribosomal protein S3 (rpS3). Journal of Biochemistry and Molecular Biology, 39: 208-215.

https://doi.org/10.5483/BMBRep.2006.39.2.208

Cobbs, C.S., Brenman, J.E., Aldape, K.D., Bredt, D.S., & Israel, M.A. (2005). Expression of nitric oxide synthase in human central nervous system tumors. Cancer Research, 55: 727-730.

Contreras-Moreira, B. & Bates, P.A. (2002). Domain Fishing: a first step in protein comparative modelling. Bioinformatics, 18: 1141-1142.

https://doi.org/10.1093/bioinformatics/18.8.1141

Donn, R.P. & Ray, D.W. (2004). Macrophage migration inhibitory factor: molecular, cellular and genetic aspects of a key neuroendocrine molecule. Journal of Endocrinology, 182: 1-9.

https://doi.org/10.1677/joe.0.1820001

Finn, R.D., Tate, J., Mistry, J., Coggill, P.C., Sammut, J.S., Hotz, H.R., Ceric, G., Forslund, K., Eddy, S.R., Sonnhammer, E.L., & Bateman, A. (2008). The Pfam protein families database. Nucleic Acids Research, Database Issue 36:D281-D288.

https://doi.org/10.1093/nar/gkm960

Fisher, E.M., Beer-Romero, P., Brown, L.G., Ridley, A., McNeil, J.A., Lawrence, J.B., Willard, H.F., Bieber, F.R., & Page, D.C. (1990). Homologous ribosomal protein genes on the human X and Y chromosomes: escape from X inactivation and possible implications for Turner syndrome. Cell, 63(6): 1205-1218.

https://doi.org/10.1016/0092-8674(90)90416-C

Gao, X., Wan, F., Mateo, K., Callegari, E., Wang, D., Deng, W., Puente, J., Li, F., Chaussee, M.S., Finlay, B.B., Lenardo, M.J., & Hardwidge, P.R. (2009). Bacterial effector binding to ribosomal protein s3 subverts NF-kappaB function. PLoS Pathogen, 5: e1000708.

https://doi.org/10.1371/journal.ppat.1000708

Gibrat, J.F., Madej, T., & Bryant, S.H. (1996). Surprising similarities in structure comparison. Current Opinion in Structural Biology, 6: 377-385.

https://doi.org/10.1016/S0959-440X(96)80058-3

Hegde, V., Yadavilli, S., McLaughlin, L.D., & Deutsch, W.A. (2009). DNA repair efficiency in transgenic mice over expressing ribosomal protein S3. Mutation Research 666: 16-22.

https://doi.org/10.1016/j.mrfmmm.2009.03.005

Henry, J.L., Coggin, D.L., & King, C.R. (1993). High-level expression of the ribosomal protein L19 in human breast tumors that overexpress erbB-2. Cancer Research, 15: 1403-1408.

Holzer, S., Ban, N., & Klinge, S. (2013). Crystal structure of the yeast ribosomal protein rps3 in complex with its chaperone Yar1. Journal of Molecular Biology, 425: 4154-4160.

https://doi.org/10.1016/j.jmb.2013.08.022

Jang, C.Y., Lee, J.Y., & Kim, J. (2004). RPS3, a DNA repair endonuclease and ribosomal protein, is involved in apoptosis. FEBS Letters, 560: 81-85.

https://doi.org/10.1016/S0014-5793(04)00074-2

Jang, C.Y., Kim, H.D., & Kim, J. (2012). Ribosomal protein S3 interacts with TRADD to induce apoptosis through caspase dependent JNK activation. Biochemical and Biophysical Research Communications, 421: 474-478.

https://doi.org/10.1016/j.bbrc.2012.04.020

Kasai, H., Nadano, D., Hidak, E., Higuchi, K., Kawakubo, M., Sato, T.A., & Nakayama, J. (2003). Differential expression of ribosomal proteins in human normal and neoplastic colorectum. Journal of Histochemistry and Cytochemistry, 51: 567-574.

https://doi.org/10.1177/002215540305100502

Kenmochi, N., Yoshihama, M., Higa, S., & Tanaka, T. (2000). The human ribosomal protein L6 gene in a critical region for Noonan syndrome. Journal of Human Genetics, 45(5): 290-293.

https://doi.org/10.1007/s100380070018

Kim, J.H., You, K.R., Kim, I.H., Cho, B.H., Kim, C.Y., & Kim, D.G. (2004). Over-expression of the ribosomal protein L36a gene is associated with cellular proliferation in hepatocellular carcinoma. Hepatology, 39: 129-138.

https://doi.org/10.1002/hep.20017

Kim, H.D., Kim, T.S., Joo, Y.J., Shin, H.S., Kim, S.H., Jang, C.Y., Lee, C.E., & Kim, J. (2010). RPS3 translation is repressed by interaction with its own mRNA. Journal of Cellular Biochemistry, 110: 294-303.

https://doi.org/10.1002/jcb.22537

Landerholm, K., Shcherbina, L., Falkmer, S.E., Järhult, J., & Wierup, N. (2012). Expression of cocaine- and amphetamine-regulated transcript is associated with worse survival in small bowel carcinoid tumors. Clinical Cancer Research, 18: 3668-3676.

https://doi.org/10.1158/1078-0432.CCR-11-2513

Lopez, C.D., Martinovsky, G., & Naumovski, L. (2002). Inhibition of cell death by ribosomal protein L35a. Cancer Letters, 180: 195-202.

https://doi.org/10.1016/S0304-3835(02)00024-1

Mao, P., Meshul, C.K., Thuillier, P., Goldberg, N.R., & Reddy, P.H. (2012). CART peptide is a potential endogenous antioxidant and preferentially localized in mitochondria. PLoS One, 7: e29343.

https://doi.org/10.1371/journal.pone.0029343

Murzin, A.G., Brenner, S.E., Hubbard, T., & Chothia, C. (1995). SCOP: A structural classification of proteins database for the investigation of sequences and structures. Journal of Molecular Biology, 247: 536-540.

https://doi.org/10.1016/S0022-2836(05)80134-2

Naora, H. (1999). Involvement of ribosomal proteins in regulating cell growth and apoptosis: translational modulation or recruitment for extraribosomal activity? Immunology and Cell Biology, 77(3): 197-205.

https://doi.org/10.1046/j.1440-1711.1999.00816.x

Peitsch, M.C. (2002). About the use of protein model. Bioinformatics, 18: 934-938.

https://doi.org/10.1093/bioinformatics/18.7.934

Pogue-Geile, K., Geiser, J.R., Shu, M., Miller, C., Wool, I.G., Meisler, A.I., & Pipas, J.M. (1991). Ribosomal protein genes are overexpressed in colorectal cancer: Isolation of a cDNA clone encoding the human S3 ribosomal protein. Molecular and Cellular Biology, 11: 3842-3849.

https://doi.org/10.1128/MCB.11.8.3842

Punta, M., & Ofran, Y. (2008). The rough guide to in silico function prediction, or how to use sequence and structure information to predict protein function. PLoS Computational Biology, 4(10): e1000160.

https://doi.org/10.1371/journal.pcbi.1000160

Roy, A., Kucukural, A., & Zhang, Y. (2010). I-TASSER: a unified platform for automated protein structure and function prediction. Nature Protocols, 5(4): 725-738.

https://doi.org/10.1038/nprot.2010.5

Ruggero, D., & Pandolfi, P.P. (2003). Does the ribosome translate cancer? Nature Reviews Cancer, 3: 179-192.

https://doi.org/10.1038/nrc1015

Sim, E.U.H., Bong, I.P.N., Balraj, P., Tan, S.K., Jamal, R., Sagap, I., Nadeson, S., Rose, I.M., & Lim, P.K.M. (2006). A preliminary study of differentially expressed genes in Malaysian colorectal carcinoma cases. Journal of Biosciences, 17: 19-37.

Sim, E.U.H., Toh, A.K.L., & Tiong, T.S. (2008). Preliminary findings of down-regulated genes in nasopharyngeal carcinoma. Asia Pacific Journal of Molecular Biology and Biotechnology, 16: 79-84.

Sim, E.U.H., Ang, C.H., Ng, C.C., Lee, C.W., & Narayanan, K. (2010). Differential expression of a subset of ribosomal protein genes in cell lines derived from human nasopharyngeal epithelium. Journal of Human Genetics, 55: 118-120.

https://doi.org/10.1038/jhg.2009.124

Vaarala, M.H., Porvari, K.S., Kyllonen, A.P., Mustonen, M.V., Lukkarinen, O., & Vihko, P.T. (1998). Several genes encoding ribosomal proteins are over-expressed in prostate cancer cell lines: confirmation of L7a and L37 over-expression in prostate-cancer tissue samples. International Journal of Cancer, 78: 27-32.

https://doi.org/10.1002/(SICI)1097-0215(19980925)78:1<27::AID-IJC6>3.0.CO;2-Z

Wan, F., Anderson, D.E., Barnitz, R.A., Snow, A., Bidere, N., Zheng, L., Hegde, V., Lam, L.T., Staudt, L.M., Leven, D., Deutsch, W.A., & Lenardo, M.J. (2007). Ribosomal protein S3: A KH domain subunit in NF-kappaB complexes that mediates selective gene regulation. Cell, 131: 927-939.

https://doi.org/10.1016/j.cell.2007.10.009

Wang, Q., Yang, C., Zhou, J., Wang, X., Wu, M., & Liu, Z. (2001). Cloning and characterization of full-length human ribosomal protein L15 cDNA which was overexpressed in esophageal cancer. Gene, 263: 205-209.

https://doi.org/10.1016/S0378-1119(00)00570-9

Wang, J., Kudoh, J., Takayanagi, A., & Shimizu, N. (2005). Novel human BTB/POZ domain-containing zinc finger protein ZNF295 is directly associated with ZFP161. Biochemical and Biophysical Research Communications, 327: 615-627.

https://doi.org/10.1016/j.bbrc.2004.12.048

Wool, I.G. (1996). Extraribosomal functions of ribosomal proteins. Trends in Biochemical Sciences, 21(5): 164-165.

https://doi.org/10.1016/S0968-0004(96)20011-8

Yadavilli, S., Mayo, L.D., Higgins, M., Lain, S., Hegde, V., & Deutsch, W.A. (2009). Ribosomal protein S3: A multi-functional protein that interacts with both p53 and MDM2 through its KH domain. DNA Repair (Amst), 8: 1215-1224.

https://doi.org/10.1016/j.dnarep.2009.07.003

Zhang, X.W., & Yap, Y.L. (2004). The 3D structure analysis of SARS-CoV S1 protein reveals a link to influenza virus neuraminidase and implications for drug and antibody discovery. Journal of Molecular Structure: THEOCHEM, 681: 137-141.

https://doi.org/10.1016/j.theochem.2004.04.065

Zhou, Y.B., Cao, J.B., Wan, B.B., Wang, X.R., Ding, G.H., Zhu, H., Yang, H.M., Wang, K.S., Zhang, X., & Han, Z.G. (2008). hBolA, novel non-classical secreted proteins, belonging to different BolA family with functional divergence. Molecular and Cellular Biochemistry, 317: 61-68.

https://doi.org/10.1007/s11010-008-9809-2

Downloads

How to Cite

Sim, E. U.-H., & Er, C.-M. (2016). Extra-Ribosomal Functions of the Ribosomal Protein, RPS3 as Predicted by In Silico Analysis. Borneo Journal of Resource Science and Technology, 4(2), 62–69. https://doi.org/10.33736/bjrst.236.2014

Issue

Section

General