The other lives of ribosomal proteins

  • Rital B. Bhavsar1,

    Affiliated with

    • Leah N. Makley1 and

      Affiliated with

      • Panagiotis A. Tsonis1Email author

        Affiliated with

        Human Genomics20104:327

        DOI: 10.1186/1479-7364-4-5-327

        Received: 29 April 2010

        Accepted: 29 April 2010

        Published: 1 June 2010

        Abstract

        Despite the fact that ribosomal proteins are the constituents of an organelle that is present in every cell, they show a surprising level of regulation, and several of them have also been shown to have other extra-ribosomal functions, such in replication, transcription, splicing or even ageing. This review provides a comprehensive summary of these important aspects.

        Keywords

        protein synthesis ribosome ribosomal proteins transcription regulation life span

        Introduction

        Protein synthesis requires accurate translation of the nucleotide sequence of messenger RNA (mRNA) to the amino acid sequence of a protein. This translation of mRNA to protein is carried out by the ribosome and transfer RNA (tRNA), along with other protein factors. In past years, studies on the structure of the ribosome have led us to understand this complex process of protein synthesis. The ribosome consists of two subunits, each of which is made up of ribosomal RNA (rRNA) and many ribosomal proteins. Structurally, ribosomes of prokaryotes and eukaryotes vary by the types of rRNA and protein molecules found in them. The prokaryotic 70S ribosome has a small 30S and a large 50S subunit. The 30S subunit consists of one 16S molecule of rRNA and about 21 proteins, while the 50S subunit consists of two rRNAs (5S and 23S) and 31 proteins. The eukaryotic 80S ribosome has a small 40S and a large 60S subunit. The 40S subunit consists of one 18S molecule of rRNA and about 33 proteins, whereas the 60S consists of three rRNAs (5S, 28S and 5.8S) and about 50 proteins [1].

        During protein synthesis, the small ribosomal subunit plays a role in accurate codon-anticodon recognition between the mRNA and tRNA molecules, while the large subunit is mainly involved in the peptide bond formation of the growing amino acid chain. In addition, structural studies of the ribosome have now revealed that they are also involved in functions such as the translocation of tRNA and mRNA on the ribosome [2].

        Apart from protein synthesis, many of the ribosomal proteins are shown to be involved in other cellular functions, independent of the ribosome [3]. Their first extra-ribosomal activity was observed for S1, as a replicase in the RNA phages, and numerous extra-ribosomal functions of these proteins have subsequently been discovered. This bifunctional tendency of ribosomal proteins can be explained by theories postulating the pre-existence of the ribosomal proteins as independent molecules before forming the components of the ribosome [3]. Another interesting functional aspect of the ribosomal proteins is their regulation. These proteins are shown to affect the mechanisms of development, apoptosis and ageing during their altered expression levels. In this review, information on the extra-ribosomal roles of these proteins is provided, along with information about their specific regulation in different cellular functions. Detailed lists of all functions and regulation are presented as Tables S1 (Table 4) and S2 (Table 5).
        Table S1

        Function and regulation of eukaryotic small subunit ribosomal proteins

        Protein Name

        Organism

        Function

        Reference

        Find online at:

        RPSA

        Porcine

        Candidate for binding and internalisation of externally added cellular prion protein in the gut

        Knorr, C., Beuermann, C., Beck, J. and Brenig, B. (2007), 'Characterization of the porcine multicopy ribosomal protein SA/37-kDa laminin receptor gene family', Gene Vol. 395(1-2), pp. 135-143.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​17434268

        RPS3A

        Human

        Cell apoptosis regulation

        Naora, H. (1999), 'Involvement of ribosomal proteins in regulating cell growth and apoptosis: Translational modulation or recruitment for extraribosomal activity?', Immunol. Cell Biol. Vol. 77, pp. 197-205.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​10361251

        RPS6

        Drosophila homologue of human S6

        Tumour suppressor in the haematopoietic system

        Watson, K.L., Konrad, K.D., Woods, D.F. and Bryant, P.J. (1992), 'Drosophila homolog of the human S6 ribosomal protein is required for tumor suppression in the hematopoietic system. Proc. Natl. Acad. Sci. USA Vol. 89, pp. 11302-11306.

        http://​www.​pubmedcentral.​nih.​gov/​articlerender.​fcgi?​artid=​50538

        RPS7

        Zebrafish

        Mutations result in malignant peripheral nerve sheath tumour (zMPNST); RP genes may be 'haploinsufficient tumour suppressors' in zebrafish and cancer genes in humans

        Amsterdam, A., Sadler, K.C., Lai, K., Farrington, S. et al. (2004), 'Many ribosomal protein genes are cancer genes in zebrafish', PLoS Biol. Vol. 2, p. E139.

        http://​biology.​plosjournals.​org/​perlserv/​?​request=​get-document&​doi=​10.​1371%2Fjournal.​pbio.​0020139&​ct=​1

        RPS8

        Zebrafish

        Mutations result in malignant peripheral nerve sheath tumour (zMPNST); RP genes may be 'haploinsufficient tumour suppressors' in zebrafish and cancer genes in humans

        Amsterdam, A., Sadler, K.C., Lai, K., Farrington, S. et al. (2004), 'Many ribosomal protein genes are cancer genes in zebrafish', PLoS Biol. Vol. 2, p. E139.

        http://​biology.​plosjournals.​org/​perlserv/​?​request=​get-document&​doi=​10.​1371%2Fjournal.​pbio.​0020139&​ct=​1

        RPS9

        Human

        Involved in retinal formation

        Uechi, T., Tanaka, T. and Kenmochi, N. (2001), 'Complete map of the human ribosomal protein genes: Assignment of 80 genes to the cytogenetic map and implications for human disorders', Genomics Vol. 72, pp. 223-230.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​11401437

        RPS10

        Arabidopsis thaliana

        Developmental regulation

        Majewski, P., Wołoszyńska, M. and Janńska, H. (2009), 'Developmentally early and late onset of Rps10 silencing in Arabidopsis thaliana: Genetic and environmental regulation', J. Exp. Bot. Vol. 60, pp. 1163-1178.

        http://​www.​pubmedcentral.​nih.​gov/​articlerender.​fcgi?​artid=​2657537&​tool=​pmcentrez

        RPS13

        Human

        Cell growth or proliferation regulation

        Lai, M.D. and Xu, J. (2007), 'Ribosomal proteins and colorectal cancer', Curr. Genomics Vol. 8, pp. 43-49.

        http://​www.​pubmedcentral.​nih.​gov/​articlerender.​fcgi?​artid=​2474683

        RPS15

        Drosophila

        Overexpression of S15a suppresses a utation in the Saccharomyces cerevisiae cdc33 gene, which encodes the cap-binding subunit of eukaryotic initiation factor 4F (eIF-4F); mutations of cdc33 lead to arrest in the cell cycle at the G1 to S transition.

        Saeboe-Larssen, S. and Lambertsson, A. (1996), 'A novel Drosophila Minute locus encodes ribosomal protein S13', Genetics Vol. 143, pp. 877-885.

        http://​www.​genetics.​org/​cgi/​reprint/​143/​2/​877

         

        Human

        Role in nuclear export of 40S subunit precursors

        Gazda, H., Sheen, M.R., Vlachos, A., Choesmel, V. et al. (2008), 'Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients', Am. J. Hum. Genet. Vol. 83, pp. 769-780.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​19061985

        RPS15A

        Zebrafish

        Mutations result in malignant peripheral nerve sheath tumour (zMPNST); RP genes may be 'haploinsufficient tumour suppressors' in zebrafish and cancer genes in humans

        Amsterdam, A., Sadler, K.C., Lai, K., Farrington, S. et al. (2004), 'Many ribosomal protein genes are cancer genes in zebrafish', PLoS Biol. Vol. 2, p. E139.

        http://​www.​pubmedcentral.​nih.​gov/​articlerender.​fcgi?​artid=​406397

        RPS18

        Arabidopsis thaliana

        Developmental regulation

        Lai, M.D. and Xu, J. (2007), 'Ribosomal proteins and colorectal cancer', Curr. Genomics Vol. 8, pp. 43-49.

        http://​www.​pubmedcentral.​nih.​gov/​articlerender.​fcgi?​artid=​2474683

         

        Arabidopsis thaliana

        Mutation in S18 associated with growth retardation and abnormal leaf development

        Naora, H. (1999), 'Involvement of ribosomal proteins in regulating cell growth and apoptosis: Translational modulation or recruitment for extraribosomal activity?', Immunol. Cell Biol. Vol. 77, pp. 197-205.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​10361251

         

        Zebrafish

        Mutations result in malignant peripheral nerve sheath tumour (zMPNST); RP genes may be 'haploinsufficient tumour suppressors' in zebrafish and cancer genes in humans

        Amsterdam, A., Sadler, K.C., Lai, K., Farrington, S. et al. (2004), 'Many ribosomal protein genes are cancer genes in zebrafish', PLoS Biol. Vol. 2, p. E139.

        http://​www.​pubmedcentral.​nih.​gov/​articlerender.​fcgi?​artid=​406397

        RPS19

        Ascaris lumbricoides

        Developmental regulation

        Lai, M.D. and Xu, J. (2007), 'Ribosomal proteins and colorectal cancer', Curr. Genomics Vol. 8, pp. 43-49.

        http://​www.​pubmedcentral.​nih.​gov/​articlerender.​fcgi?​artid=​2474683

         

        Human

        Tumour progression, invasion, metastasis, differentiation'

        Lai, M.D. and Xu, J. (2007), 'Ribosomal proteins and colorectal cancer', Curr. Genomics Vol. 8, pp. 43-49.

        http://​www.​pubmedcentral.​nih.​gov/​articlerender.​fcgi?​artid=​2474683

         

        Human

        Degeneration of retina

        Uechi, T., Tanaka, T. and Kenmochi, N. (2001), 'Complete map of the human ribosomal protein genes: Assignment of 80 genes to the cytogenetic map and implications for human disorders', Genomics Vol. 72, pp. 223-230.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​11401437

         

        Human

        Dimer acts as a monocyte chemotactic factor in phagocytic clearance of apoptotic cells

        Naora, H. (1999), 'Involvement of ribosomal proteins in regulating cell growth and apoptosis: Translational modulation or recruitment for extraribosomal activity?', Immunol. Cell Biol. Vol. 77, pp. 197-205.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​10361251

         

        Zebrafish

        Haematopoietic and developmental abnormalities

        Danilova, N., Sakamoto, K.M. and Lin, S. et al. (2008), 'Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family', Blood Vol. 112, pp. 5228-5537.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​18515656

        RPS20

        Yeast

        Overexpression of S20 suppresses temperature-sensitive RNA pol III (but no specificity?)

        Hermann-Le Denmat, S., Sipiczki, M. and Thuriaux, P. (1994), 'Suppression of yeast RNA polymerase III mutations by the URP2 gene encoding a protein homologous to the mammalian ribosomal protein S20', J. Mol. Biol. Vol. 240, pp. 1-7.

        http://​www.​sciencedirect.​com/​science?​_​ob=​ArticleURL&​_​udi=​B6WK7-45PV62P-1S&​_​user=​4887109&​_​rdoc=​1&​_​fmt=​&​_​orig=​search&​_​sort=​d&​view=​c&​_​acct=​C000062864&​_​version=​1&​_​urlVersion=​0&​_​userid=​4887109&​md5=​88a77e1986f7765e​9374d649cc9b23a8​

         

        Human

        mRNA downregulated in onset of apoptosis in leukaemic cells

        Naora, H. (1999), 'Involvement of ribosomal proteins in regulating cell growth and apoptosis: Translational modulation or recruitment for extraribosomal activity?', Immunol. Cell Biol. Vol. 77, pp. 197-205.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​10361251

        RPS21

        Drosophila

        Acts as a translation initiation factor rather than as a core ribosomal protein

        Török, I., Herrmann-Horle, D., Kiss, I., Tick, G. et al. (1999), 'Down-regulation of RpS21, a putative translation initiation factor interacting with P40, produces viable minute imagos and larval lethality with overgrown hematopoietic organs and imaginal discs', Mol. Cell Biol. Vol. 19, pp. 2308-2321.

        http://​www.​pubmedcentral.​nih.​gov/​articlerender.​fcgi?​artid=​84023&​tool=​pmcentrez

        RPS27A

        Human

        Cell growth or proliferation regulation

        Ye, J.L. and Zhang, Y.Z. (2007), 'The connection between tumor and ubiquitin-ribosomal protein S27a, ubiquitin and ribosomal protein', Sheng Wu Gong Cheng Xue Bao Vol. 23, pp. 982-988. [Article in Chinese]

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​18257223?​ordinalpos=​5&​itool=​EntrezSystem2.​PEntrez.​Pubmed.​Pubmed_​ResultsPanel.​Pubmed_​DefaultReportPan​el.​Pubmed_​RVDocSum

         

        Human

        Cell growth or proliferation regulation

        Lai, M.D. and Xu, J. (2007), 'Ribosomal proteins and colorectal cancer', Curr. Genomics Vol. 8, pp. 43-49.

        http://​www.​pubmedcentral.​nih.​gov/​articlerender.​fcgi?​artid=​2474683

         

        Human

        Cell malignant transformation

        Ye, J.L. and Zhang, Y.Z. (2007), 'The connection between tumor and ubiquitin-ribosomal protein S27a, ubiquitin and ribosomal protein', Sheng Wu Gong Cheng Xue Bao Vol. 23, pp. 982-988. [Article in Chinese]

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​18257223?​ordinalpos=​5&​itool=​EntrezSystem2.​PEntrez.​Pubmed.​Pubmed_​ResultsPanel.​Pubmed_​DefaultReportPan​el.​Pubmed_​RVDocSum

        RPS28

        Yeast

        Binds to the 3' UTR of its mRNA to stimulate its deadenylation and degradation

        Badis, G., Saveanua, C., Fromont-Racinea, M. and Jacquie, A. (2004), 'Targeted mRNA degradation by deadenylation-independent decapping', Mol. Cell Vol. 15, pp. 5-15.

        http://​www.​sciencedirect.​com/​science?​_​ob=​ArticleURL&​_​udi=​B6WSR-4CRXKG3-3&​_​user=​4887109&​_​rdoc=​1&​_​fmt=​&​_​orig=​search&​_​sort=​d&​view=​c&​_​acct=​C000062864&​_​version=​1&​_​urlVersion=​0&​_​userid=​4887109&​md5=​9b5ba025da819e72​5850644ba547d47c​

        RPS29

        Human

        Tumour suppression gene regulation

        Lai, M.D. and Xu, J. (2007), 'Ribosomal proteins and colorectal cancer', Curr. Genomics Vol. 8, pp. 43-49.

        http://​www.​pubmedcentral.​nih.​gov/​articlerender.​fcgi?​artid=​2474683

         

        Human

        Increases tumour supporessor activity of Krev-1'

        Naora, H. (1999), 'Involvement of ribosomal proteins in regulating cell growth and apoptosis: Translational modulation or recruitment for extraribosomal activity?', Immunol. Cell Biol. Vol. 77, pp. 197-205.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​10361251

         

        Zebrafish

        Mutations result in malignant peripheral nerve sheath tumour (zMPNST); RP genes may be 'haploinsufficient tumour suppressors' in zebrafish and cancer genes in humans

        Amsterdam, A., Sadler, K.C., Lai, K., Farrington, S. et al. (2004), 'Many ribosomal protein genes are cancer genes in zebrafish', PLoS Biol. Vol. 2, p. E139.

        http://​www.​pubmedcentral.​nih.​gov/​articlerender.​fcgi?​artid=​406397

        Date last accessed for all websites is 17th June, 2010

        Table S2

        Function and regulation of eukaryotic large subunit ribosomal proteins

        Protein Name

        Organism

        Function

        Reference

        Find online at

        RPL4

        Rat

        Required for rapid neurite regeneration

        Twiss, J.L., Smith, D.S., Chang, B. and Shooter, E.M. (2000), 'Translational control of ribosomal protein L4 mRNA is required for rapid neurite regeneration', Neurobiol. Dis. Vol. 7, pp. 416-428.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​10964612

         

        S. cerevisiae

        Binds to single-stranded RNA/DNA

        Cusick, M.E. (1994), 'Purification and identification of two major single-stranded binding proteins of yeast Saccharomyces cerevisiae as ribosomal protein L4 and histone H2B', Biochim. Biophys. Acta. Vol. 1217, pp. 31-40.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​8286414

        RPL7A

        Human

        Part of chimeric protein encoded by trk-2h oncogene

        Ziemiecki, A., Müller, R.G., Fu, X.C., Hynes, N.E. et al. (1990), 'Oncogenic activation of the human trk proto-oncogene by recombination with the ribosomal large subunit protein L7a', EMBO J. Vol. 9, pp. 191-196.

        http://​www.​ncbi.​nlm.​nih.​gov/​pmc/​articles/​PMC551645/

         

        Zebrafish

        Categorised as an ocular gene; downregulated in eyeless masterblind zebrafish.

        Wang, H., Kesinger, J.W., Zhou, Q., Wren, J.D. et al. (2008), 'Identification and characterization of zebrafish ocular formation genes', Genome Vol. 51, pp. 222-235.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​18356958

        RPL7

        Human

        Coregulator of vitamin D receptor-retinoid X receptor-mediated transactivation of genes

        Berghöfer-Hochheimer, Y., Zurek, C., Wölfl, S., Hemmerich, P. et al. (1998), 'L7 protein is a coregulator of vitamin D receptor-retinoid X receptor-mediated transactivation', J. Cell. Biochem. Vol. 69, pp. 1-12.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​9513041

         

        Rana sylvatica

        Upregulated under freezing conditions

        Wu, S., De Croos, J.N. and Storey, K.B. (2008), 'Cold acclimation-induced up-regulation of the ribosomal protein L7 gene in the freeze tolerant wood frog, Rana sylvatica', Gene Vol. 424, pp. 48-55.

        http://​www.​sciencedirect.​com/​science?​_​ob=​ArticleURL&​_​udi=​B6T39-4T3DCV0-1&​_​user=​4887109&​_​coverDate=​11%2F15%2F2008&​_​rdoc=​1&​_​fmt=​high&​_​orig=​search&​_​sort=​d&​_​docanchor=​&​view=​c&​_​searchStrId=​1246451135&​_​rerunOrigin=​google&​_​acct=​C000062864&​_​version=​1&​_​urlVersion=​0&​_​userid=​4887109&​md5=​4e11f74a6e6a29fe​16aa172087195d0d​

        RPL10

        Arabidopsis

        A component of the NIK-mediated antiviral signaling

        Rocha, C.S., Santos, A.A., Machado, J.P. and Fontes, E.P. (2008), 'The ribosomal protein L10/QM-like protein is a component of the NIK-mediated antiviral signaling', Virology Vol. 380, pp. 165-169.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​18789471

        RPL13

        Hamster cells

        Upregulated in response to DNA damage

        Kobayashi, T., Sasaki, Y., Oshima, Y., Yamamoto, H. et al. (2006), 'Activation of the ribosomal protein L13 gene in human gastrointestinal cancer', Int. J. Mol. Med. Vol. 18, pp. 161-170.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​16786168

        RPL22

        Mammals

        Identical to heparin-binding protein, HBp15

        Fujita, Y., Okamoto, T., Noshiro, M., McKeehan, W.L. et al. (1994), 'A novel heparin-binding protein, HBp15, is identified as mammalian ribosomal protein L22', Biochem. Biophys. Res. Commun. Vol. 199, pp. 706-713.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​8135813

         

        Drosophila

        Interacts with casein kinase II

        Zhao, W., Bidwai, A.P. and Glover, C.V. (2002), 'Interaction of casein kinase II with ribosomal protein L22 of Drosophila melanogaster', Biochem. Biophys. Res. Commun. Vol. 298, pp. 60-66.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​12379220

         

        Human

        Binds Epstein-Barr virus (EBV)-encoded RNA (EBER) in EBV-infected cells

        Le, S., Sternglanz, R. and Greider, C.W. (2000), 'Identification of two RNA-binding proteins associated with human telomerase RNA', Mol. Biol. Cell Vol. 11, pp. 999-1010.

        http://​www.​ncbi.​nlm.​nih.​gov/​pmc/​articles/​PMC14826/

         

        Human

        Binds human telomerase RNA

        Le, S., Sternglanz, R. and Greider, C.W. (2000), 'Identification of two RNA-binding proteins associated with human telomerase RNA', Mol. Biol. Cell Vol. 11, pp. 999-1010.

        http://​www.​ncbi.​nlm.​nih.​gov/​pmc/​articles/​PMC14826/​

        RPL23A

        Human

        May play a role in growth inhibition

        Jiang, H., Lin, J.J., Tao, J. and Fisher, P.B. (1997), 'Suppression of human ribosomal protein L23A expression during cell growth inhibition by interferon-beta', Oncogene Vol. 14, pp. 473-480.

        http://​www.​nature.​com/​onc/​journal/​v14/​n4/​abs/​1200858a.​html

        RPL24

        Arabidopsis

        Gynoecium development

        Nishimura, T., Wada, T. and Okada, K. (2004), 'A key factor of translation reinitiation, ribosomal protein L24, is involved in gynoecium development in Arabidopsis', Biochem. Soc. Trans. Vol. 32, pp. 611-613.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​15270688?​dopt=​Abstract

         

        Marine shrimp

        Differential expression in gonads

        Zhang, Z., Wang, Y., Jiang, Y., Lin, P. et al. (2007), 'Ribosomal protein L24 is differentially expressed in ovary and testis of the marine shrimp Marsupenaeus japonicus', Comp. Biochem. Physiol. B Biochem. Mol. Biol. Vol. 147, pp. 466-474.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​17462931

        RPL35A

        Human

        Cell death inhibition

        Lopez, C.D., Martinovsky, G. and Naumovski, L. (2002), 'Inhibition of cell death by ribosomal protein L35a', Cancer Lett. Vol. 180, pp. 195-202.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​12175552

        RPP0

        Human

        Interacts with GCIP, and over-expression in breast and liver cancer results in cell proliferation

        Chang, T.W., Chen, C.C., Chen, K.Y., Su, J.H. et al. (2008), 'Ribosomal phosphoprotein P0 interacts with GCIP and overexpression of P0 is associated with cellular proliferation in breast and liver carcinoma cells', Oncogene Vol. 27, pp. 332-338.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​17621266

        RPLP1

        Mouse

        Over-expression leads to cell proliferation of mouse embryonic fibroblasts

        Artero-Castro, A., Kondoh, H., Fernández-Marcos, P.J., Serrano, M. et al. (2009), 'Rplp1 bypasses replicative senescence and contributes to transformation', Exp. Cell Res. Vol. 315, pp. 1372-1383.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​19233166

        MRPL41

        Human and mice

        Suppresses cell growth

        Yoo, Y.A., Kim, M.J., Park, J.K., Chung, Y.M. et al. (2005), 'Mitochondrial ribosomal protein L41 suppresses cell growth in association with p53 and p27Kip1', Mol. Cell. Biol. Vol. 25, pp. 6603-6616.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​16024796

        Date last accessed for all websites is 17th June, 2010

        Extra-ribosomal properties of the ribosomal proteins

        Ribosomal proteins and gene expression

        Temporal regulation of gene expression is critical for cell survival and function. Chromatin modification, transcription, translation, RNA processing and post-translational modification are the major checkpoints for a cell to regulate gene expression. Many of the prokaryotic and eukaryotic ribosomal proteins are involved in the regulation of their own expression or expression of other genes at different levels of gene regulation (Table 1).
        Table 1

        Ribosomal proteins involved in gene regulation mechanisms

        Gene regulation level

        Ribosomal protein (RP)

        Organism

        Function

        Reference

        Chromatin

        S2

        Escherichia coli

        Negative regulator of rpsB and tsf expression

        4

         

        S3

        Homo sapiens

        Becomes a part of nuclear factor-κB complex that interacts with specific sites in the genome, on tumour necrosis factor stimulation

        6

         

        S4

        Bacillus subtilis

        Autoregulates rpsD gene expression

        5

         

        L13a

        H. sapiens

        Inflammatory gene expression

        7

        Transcription

        S1

        E. coli

        Transcription anti-termination and stimulates transcriptional activity of RNA polymerase

        8,9

         

        S4

        E. coli

        Transcription anti-termination

        10

         

        S10

        E. coli

        Transcription anti-termination

        11

         

        L3

        E. coli

        Transcription anti-termination

        10

         

        L4

        E. coli

        Inhibits transcription of S10 operon mRNA and transcription anti-termination

        3,10

         

        S14

        H. sapiens

        Self-regulation at both transcriptional and translational levels

        3,12

         

        S20

        Saccharomyces cerevisiae

        Transcription anti-termination

        3

         

        S0 and S21 (in association with each other)

        S. cerevisiae

        Promote maturation of 3' end of 18S rRNA

        13

         

        L11

        Rattus rattus

        Inhibits the transcriptional activity of peroxisome proliferator-activated receptor-alpha, a nuclear receptor

        14

         

        L13

        E. coli

        Transcription anti-termination

        10

        Post-transcription

        S14

        S. cerevisiae

        Post-transcriptional repression of RPS14B [CRY2] expression

        15

        RNA processing and splicing

        S12

        E. coli

        Acts as RNA chaperone in the folding process of T4 phage intron RNA

        16

         

        S12

        H. sapiens

        RNA splicing and modification

        12

         

        S13

        S. cerevisiae and H. sapiens

        Binds to the first intron of its transcript to inhibit splicing.

        Overproduction of RPS13 interferes with splicing of its own pre-mRNA by a feedback mechanism.

        Negatively controls splicing of its own pre-mRNA

        17,18

         

        S14

        H. sapiens

        Required for 18S pre-RNA processing and 40S subunit formation

        19

         

        L4

        Mus musculus

        Interacts with Gu(alpha) which is involved in rRNA processing

        20

        Translation

        S4

        E. coli

        Translational repressor of α operon (operon genes; S13, S11, S4, L17)

        21

         

        S8

        E. coli

        Translational repressor of spc operon

        22

         

        S15

        E. coli

        Self-translation regulation

        23

         

        L1

        E. coli

        Self-translation regulation

        12

         

        L4

        E. coli

        Suppresses translation of S10 operon mRNA.

        Self-translation regulation

        3,12

         

        L10

        E. coli

        Self-translation regulation

        12

         

        S26

        H. sapiens

        Self-translation regulation

        12

         

        S30

        S. cerevisiae

        Self-translation regulation

        12

         

        L13a

        H. sapiens

        Silence translation of ceruloplasmin (Cp) mRNA

        24

        Post-translation

        S20

        E. coli

        Post-translational inhibition of ornithine and arginine decarboxylase enzymes

        25

        Ribosomal proteins and nucleic acid replication

        During viral infection, viruses recruit some of the host machinery in order to produce new viral particles. The synthesis of new viral particles requires the replication of the viral genome, and in most of the DNA viruses the duplication of their genome is carried out by the host replication system. Ribosomal proteins are shown to take part in the genome replication in both DNA and RNA viruses. The ribosomal protein L14 helps Rep helicase to unwind the DNA during replication of the bacteriophage genome[12], and S1 is a subunit of Qβ replicase that replicates the genome of RNA coliphage Qβ [3]. In yeast, L3 helps in replication or maintenance of the double-stranded RNA genome [26].

        Ribosomal proteins and DNA repair

        Any damage to DNA disrupts the genome's integrity and thus proves fatal to the cell. The causes of such DNA damage are either metabolic processes within the cell or environmental factors like radiation/mutagens. Several DNA repair mechanisms exist within the cell to correct DNA damage. The type of mechanism employed is determined, in turn, by the type of damage. Ribosomal proteins are shown to function in DNA repair mechanisms in both prokaryotes and eukaryotes (Table 2).
        Table 2

        Ribosomal proteins in DNA repair mechanisms

        Ribosomal protein

        Organism

        Function

        Reference

        S9

        E. coli

        Involved in SOS repair mechanism by participating with polymerase UmuC

        3

        S3

        Drosophila spp.

        DNA repair endonuclease. Corrects damage resulting from oxidative and ionising radiation

        27

         

        H. sapiens

        Knockdown of S3 protects human cells from genotoxic stress.

        This is the converse of the situation in Drosophila S3

        28

        P0/LP0 (constituent of ribosomal stalk structure)

        Drosophila, H. sapiens

        Apurinic/apyrimidinic endonuclease activity

        29

        Regulation of ribosomal proteins

        Ribosomal proteins and the cell cycle

        The cell undergoes different phases of growth and division during the cell cycle. The progression of a cell through these phases is controlled by cyclin/cyclin-dependent kinases (Cdk) and regulatory molecules of cell cycle checkpoints. Ribosomal proteins have been shown to alter the cell cycle fate by interacting with these molecules as an extra-ribosomal function. Human L34 inhibits the cell cycling proteins Cdk4 and Cdk5 [30]. L26 binds to the 5' untranslated region (UTR) of p53 mRNA upon DNA damage and increases translation of p53, a key player in cell cycle regulation and apoptosis [31].

        Many of the other ribosomal proteins function to control the cell cycle and apoptosis through their expression levels. Abnormal expression levels of L7[32] and L13a[33] in humans interfere with cell cycle progression by arresting the cell cycle and inducing apoptosis. The involvement of ribosomal proteins in apoptosis is further evidenced by their interaction with Mdm2, a ubiquitin ligase that keeps a check on P53 levels under normal cellular conditions. The mammalian ribosomal protein L26 interacts with Mdm2 and thus regulates p53 levels [34]. Many more eukaryotic ribosomal proteins (S7, S19, S20, S27L, L5, L22 and L23) function in p53-mediated apoptosis [3538]. In humans, the ribosomal protein S3 is shown to induce caspase-dependent apoptosis [12]. Also, some of the ribosomal proteins involved in apoptosis are over-expressed in cancers (Table 3).
        Table 3

        Expression pattern of ribosomal proteins in cancers

        Ribosomal protein

        Expression pattern

        Cancer type

        Reference

        S2

        Over-expressed

        Prostate cancer, head and neck carcinomas

        39,40

        S3, S6, S8, S12

        Over-expressed

        Colon cancer

        40

        S3A, S4, S17

        Over-expressed

        Feline leukaemia virus-induced lymphomas

        40

        S11

        Over-expressed

        Colorectal cancer

        41

        L7A

        Over-expressed

        Colorectal cancer

        42

         

        Under-expressed

        Osteosarcoma

        43

        L13

        Over-expressed

        Gastrointestinal cancer

        44

        L15

        Over-expressed

        Oesophageal cancer

        45

         

        Over-expressed

        Gastric cancer

        46

        L19

        Over-expressed

        Human breast cancer Used as marker for human prostate cancer

        47,48

        L23A, L27, L30

        Over-expressed

        Hepatocellular carcinoma

        49

        L30

        Over-expressed

        Medulloblastoma

        50

        Ribosomal proteins and disease

        Any defects in ribosomal proteins affect the synthesis of proteins that are required by a cell for carrying out vital cellular functions. Apart from protein synthesis, some of the ribosomal proteins are implicated in disease conditions owing to abnormal expression levels or expression of mutated genes. A mutation in ribosomal protein S19 was initially characterised as the cause of Diamond-Blackfan anaemia (DBA), a congenital erythroid aplasia [51]. Subsequently, ribosomal proteins S17, S15, S24, S7, L5 and L11 were also found to be involved in DBA [52]. It also has been shown that ribosomal proteins S3A (mouse) and S19 (zebrafish) function in erythropoiesis [18, 53]. The function of these ribosomal proteins in erythropoiesis and DBA might give some clues as to how defects in the ribosomal proteins lead to the low red blood cell count in DBA patients.

        In some disease conditions, the expression levels of the ribosomal proteins play an important role, as in Turner syndrome and human cataracts. Turner syndrome has been linked to a deficiency in human ribosomal proteins 4X and 4Y (isoforms of rps4)[54], and expression of L7A, L15 and L21 is downregulated in human cataracts [55]. A similar syndrome, named Noonan's syndrome, has been linked to ribosomal protein gene rpl6. This gene was found to be located in the same chromosome locus as Noonan's syndrome [56]. Other ribosomal proteins, such as S14, L24 and S26, are associated with 5q syndrome, mouse Bst and diabetes, respectively [19, 57, 58].

        Ribosomal proteins and developmental regulation

        During the development of an organism, the cells undergo growth and differentiation to give rise to tissues and organs. These processes are regulated by spatial and temporal control of gene expression. The ribosomal proteins that are involved in protein synthesis are also found to regulate development in many species. In Arabidopsis, some of the ribosomal protein genes are termed embryo defective, as mutated forms of these genes are lethal to embryo development [59]. A similar study in zebrafish has shown that ribosomal protein L11 affects embryological development in this species [60]. In animals, ribosomal proteins are involved in processes such as oogenesis and gonad development. The ribosomal protein S2 in Drosophila melanogaster and S15A in sea urchins play a role in oogenesis, while S4 in human is involved in gonad development [3]. Developmental defects in genes such as Drosophila minutes, mouse Bst (belly spot and tail), which encodes rpL24, and Dsk (dark skin mutants), which encodes rpS19, are also the result of defective ribosomal proteins. Organisms with these conditions exhibit various growth defects and have reduced adult size.

        Since protein synthesis is the essential process that needs to be regulated during development, expression levels of ribosomal proteins are also regulated during the different developmental stages (Figure 1). Any change in this expression profile thus affects the protein machinery that is necessary for the normal development of an organism.
        http://static-content.springer.com/image/art%3A10.1186%2F1479-7364-4-5-327/MediaObjects/40246_2010_Article_236_Fig1_HTML.jpg
        Figure 1

        ( a ) rps4x transcription profile during zebrafish development. (b) rp///transcription profile during zebrafish development. See the Array Express Archive from the European Bioinformatics Institute: http://​www.​ebi.​ac.​uk/​;http://​www.​ebi.​ac.​uk/​microarray-as/​ae/​(accessed 23rd March, 2010).

        Ribosomal proteins and lifespan regulation

        Many recent studies have come up with different mechanisms by which an organism regulates its life span. The insulin/insulin-like growth factor 1 signalling (IIS) pathway and caloric restriction (CR) has been the major players of lifespan regulation in many species [61]. In the insulin signalling pathway, the components of this pathway, such as abnormal DAuer Formation (DAF)-2 or the downstream factor DAF-16, regulate the expression of various genes involved in metabolism, the stress response and other processes that shorten life span [61, 62]. In CR, the life span of an organism is increased by decreasing the caloric intake. There is not much evidence of the mechanism by which CR affects the life span but some genes have been identified in Caenorhabditis elegans that influence life span regulation through CR [61]. It is further observed that the genes involved in CR mechanism are also linked to the IIS pathway [63, 64]. Another player of longevity is the nutrient-responsive pathway mammalian target of rapamycin (mTOR) [65]. Both IIS and mTOR have a common downstream factor, ribosomal protein S6 kinase 1, which functions in regulating the mammalian life span [66]. Thus, these different pathways interact with each other to regulate longevity.

        Also, many of the genes essential for growth and development are shown to extend the life span of a wide range of organisms. Among these genes are those involved in protein synthesis. The inactivation of translation initiation factors and ribosomal proteins S3, S8 and S11 was observed to increase the mean life span in Caenorhabditis elegans [61]. This indicates that the cell conserves its energy by keeping a check on protein synthesis.

        Clearly, ribosomal proteins have additional functions outside the ribosome which are also regulated. One would expect that this would not be the case for such 'housekeeping' factors (indeed, several ribosomal protein genes are used as controls to normalise for gene regulation). Why does such regulation exist, and is it important? One answer could be that differential regulation might slow or speed up the process of protein synthesis. In the case of life span extension, it seems that downregulation of protein synthesis is involved. Another interesting aspect is how these extra-ribosomal functions have evolved; one possibility is via gene duplication, something that has been suggested for plant development and also in yeast [38, 59]. These properties provide an important evolutionary paradigm in which nature uses existing genes for diversification.
        Table S3

        Function and regulation of prokaryotic small subunit ribosomal proteins

        Protein Name

        Organism

        Function

        Reference

        Find online at

        RPS1

        E. coli

        Stimulates the T4 endo-ribonuclease Reg B

        Aliprandi et al., S1 Ribosomal Protein Functions in Translation Initiation and Ribonuclease RegB Activation are mediated by similar RNA-Protein Interactions. (2008). The Journal of Biological Chemistry 283(19):13289-13301.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​18211890

          

        Poly (A) binding protein in E. coli

        Kalapos MP, Paulus H, Sarkar N. (1997). Identification of ribosomal protein S1 as a poly(A) binding protein in Escherichia coli. Biochimie 79(8):493-502.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​9451450

          

        Interact with non-coding RNA DsrA and with rpoS mRNA and has a small role in altering the structures of these RNAs

        Rositsa I. Koleva, Christina A. Austin, Jeffrey M. Kowaleski, Daniel S. Neems, Leyi Wang, Calvin P.H. Vary, Paula Jean Schlax. (2006). Interactions of ribosomal protein S1 with DsrA and rpoS mRNA. Biochemical and Biophysical Research Communications 348: 662-668.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​16890206

          

        Binds to tmRNA, which tags truncated/trans-translated proteins for degradation

        Matthieu Saguy, Reynald Gillet, Patricia Skorski, Sylvie Hermann-Le Denmat and Brice Felden. (2007). Ribosomal protein S1 influences trans-translation in vitro and in vivo. Nucleic Acids Research 35(7): 2368-2376.

        http://​nar.​oxfordjournals.​org/​cgi/​content/​abstract/​gkm100v1

          

        Over expression results in protection of mRNA degradation by PNPase

        Briani et al.; (2008). Polynucleotide phosphorylase hinders mRNA degradation upon ribosomal protein S1 overexpression in Escherichia coli. RNA 4(11):2417-2429.

        http://​rnajournal.​cshlp.​org/​content/​14/​11/​2417.​abstract

        RPS3

        E. coli

        Identical to H-protein in E. coli (Binds DNA and is associated with E. coli nucleoid)

        Robert C.Bruckner and Michael M.Cox. (1989). The histone-like H protein of Escherichia coli is ribosomal protein S3. Nucleic Acids Research 17(8).

        http://​nar.​oxfordjournals.​org/​cgi/​content/​abstract/​17/​8/​3145

        RPS4

        E. coli

        Overproduction of S4 stimulate rRNA synthesis

        Takabe, Y., Miura, A., Bedwell, D., Tam, M. and Nomura, M. (1985). Increased expression of ribosomal genes during inhibition of ribosome assembly in Escherichia coli. Journal of Molecular Biology 184: 23-30.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​3897554

        RPS6

        Myxococcus xanthus

        Heat inducible protein

        Maria De Angelis, Raffaella Di Cagno, Claude Huet, Carmine Crecchio, Patrick F. Fox, and Marco Gobbetti. (2004). Heat Shock Response in Lactobacillus plantarum. Applied and Environmental Microbiology 70 (3): 1336-1346.

        http://​aem.​asm.​org/​cgi/​content/​abstract/​70/​3/​1336

        RPS16

        E. coli

        Acts as an endonuclease

        Jacques Oberto, Eliette Elisabeth Mouray, Olivier Pellegrini, P. Mikael Wikstrom and Josette Rouviere-Yaniv. (1996). The Escherichia coli ribosomal protein S16 is an Endonuclease. Molecular Microbiology 19(6): 1319-1330.

        http://​www3.​interscience.​wiley.​com/​journal/​119219619/​abstract

        Table S4

        Function and regulation of prokaryotic large subunit ribosomal proteins

        Protein Name

        Organism

        Function

        Reference

        Find online at

        RPL2

        E. coli

        Zinc-binding protein

        Katayama A, Tsujii A, Wada A, Nishino T, Ishihama A. Systematic search for zinc-binding proteins in Escherichia coli Eur. J. Biochem. 269(9):2403-2413.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​11985624?​ordinalpos=​2&​itool=​EntrezSystem2.​PEntrez.​Pubmed.​Pubmed_​ResultsPanel.​Pubmed_​DefaultReportPan​el.​Pubmed_​RVDocSum

        RPL4

        E. coli

        Allosterically regulates RNase E-dependent RNA degradation 'inhibiting RNase E-specific cleavage in vitro, stabilising mRNAs targeted by RNase E in vivo, and controlling plasmid DNA replication by stabilizing an antisense regulatory RNA normally attacked by RNase E' also upregulated in stress, which accompanies inactivation of RNase E and increased half-life of stress-responsive transcripts

        Singh D, Chang SJ, Lin PH, Averina OV, Kaberdin VR, Lin-Chao S. (2009), Regulation of ribonuclease E activity by the L4 ribosomal protein of Escherichia coli. Proc. Natl. Acad. Sci. USA. 106(3):864-869. Epub 2009 Jan 14.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​19144914?​ordinalpos=​1&​itool=​EntrezSystem2.​PEntrez.​Pubmed.​Pubmed_​ResultsPanel.​Pubmed_​DefaultReportPan​el.​Pubmed_​RVDocSum

        RPL11

        E. coli

        Involved in regulating the activity of (p)ppGpp synthetase I

        Yang X, Ishiguro EE. (2001), Involvement of the N terminus of ribosomal protein L11 in regulation of the RelA protein of Escherichia coli. J. Bacteriol. 183(22):6532-6537.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​11673421?​ordinalpos=​7&​itool=​EntrezSystem2.​PEntrez.​Pubmed.​Pubmed_​ResultsPanel.​Pubmed_​DefaultReportPan​el.​Pubmed_​RVDocSum

        RPL13

        E. coli

        Zinc binding protein

        Katayama A, Tsujii A, Wada A, Nishino T, Ishihama A. Systematic search for zinc-binding proteins in Escherichia coli. Eur. J. Biochem. 269(9):2403-2413.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​11985624?​ordinalpos=​2&​itool=​EntrezSystem2.​PEntrez.​Pubmed.​Pubmed_​ResultsPanel.​Pubmed_​DefaultReportPan​el.​Pubmed_​RVDocSum

        RPL25

        E. coli/Bacillus subtilis

        General stress protein Ctc: might be required for accurate translation under stress conditions

        Schmalisch M, Langbein I, Stülke J. (2002), The general stress protein Ctc of Bacillus subtilis is a ribosomal protein. J. Mol. Microbiol. Biotechnol. 4(5):495-501.

        http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​12432960?​ordinalpos=​1&​itool=​EntrezSystem2.​PEntrez.​Pubmed.​Pubmed_​ResultsPanel.​Pubmed_​DiscoveryPanel.​Pubmed_​Discovery_​RA&​linkpos=​2&​log$=​relatedarticles&​logdbfrom=​pubmed

        Authors’ Affiliations

        (1)
        Department of Biology, University of Dayton

        References

        1. Lodish H, Berk A, Zipursky SL, Matsudaira P, et al: Molecular cell biology. 2000, W.H. Freeman and Co., New York, NY, 4
        2. Zimmermann RA: The double life of ribosomal proteins. Cell. 2003, 115: 130-132. 10.1016/S0092-8674(03)00804-3.View ArticlePubMed
        3. Wool IG: Extraribosomal functions of ribosomal proteins. Trends Biochem Sci. 1996, 21: 164-165.View ArticlePubMed
        4. Aseev LV, Levandovskaya AA, Tchufistova LS, Scaptsova NV, et al: A new regulatory circuit in ribosomal protein operons: S2-mediated control of the rpsB-tsf expression in vivo. RNA. 2008, 14: 1882-1894. 10.1261/rna.1099108.PubMed CentralView ArticlePubMed
        5. Grundy FJ, Henkin TM: The rpsd gene, encoding ribosomal-protein S4, is autogenously regulated in Bacillus subtilis. J Bacteriol. 1991, 173: 4595-4602.PubMed CentralPubMed
        6. Wan F, Anderson DE, Barnitz RA, Snow A, et al: Ribosomal protein S3: A KH domain subunit in NF-kappaB complexes that mediates selective gene regulation. Cell. 2007, 131: 927-939. 10.1016/j.cell.2007.10.009.View ArticlePubMed
        7. Mukhopadhyay R, Ray PS, Arif A, Brady AK, et al: DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression. Mol Cell. 2008, 32: 371-382. 10.1016/j.molcel.2008.09.019.PubMed CentralView ArticlePubMed
        8. Mogridge J, Greenblatt J: Specific binding of Escherichia coli ribosomal protein S1 to boxA transcriptional antiterminator RNA. J Bacteriol. 1998, 180: 2248-2252.PubMed CentralPubMed
        9. Sukhodolets MV, Garges S: Interaction of Escherichia coli RNA polymerase with the ribosomal protein S1 and the Sm-like ATPase Hfq. Biochemistry. 2003, 42: 8022-8034. 10.1021/bi020638i.View ArticlePubMed
        10. Torres M, Condon C, Balada JM, Squires C, et al: Ribosomal protein S4 is a transcription factor with properties remarkably similar to NusA, a protein involved in both non-ribosomal and ribosomal RNA antitermination. EMBO J. 2001, 20: 3811-3820. 10.1093/emboj/20.14.3811.PubMed CentralView ArticlePubMed
        11. Warren F, Das A: Formation of termination-resistant transcription complex at phage-lambda nut locus: Effects of altered translation and a ribosomal mutation. Proc Natl Acad Sci USA. 1984, 81: 3612-3616. 10.1073/pnas.81.12.3612.PubMed CentralView ArticlePubMed
        12. Lai MD, Xu J: Ribosomal proteins and colorectal cancer. Curr Genomics. 2007, 8: 43-49. 10.2174/138920207780076938.PubMed CentralView ArticlePubMed
        13. Tabb-Massey A, Caffrey JM, Logsden P, Taylor S, et al: Ribosomal proteins Rps0 and Rps21 of Saccharomyces cerevisiae have overlapping functions in the maturation of the 3' end of 18S rRNA. Nucleic Acids Res. 2003, 31: 6798-6805. 10.1093/nar/gkg899.PubMed CentralView ArticlePubMed
        14. Gray JP, Davis JW, Gopinathan L, Leas TL, et al: The ribosomal protein rpL11 associates with and inhibits the transcriptional activity of peroxisome proliferator-activated receptor-alpha. Toxicol Sci. 2006, 89: 535-546. 10.1093/toxsci/kfj040.View ArticlePubMed
        15. Li Z, Paulovich AG, Woolford JL: Feedback inhibition of the yeast ribosomal protein gene CRY2 is mediated by the nucleotide sequence and secondary structure of CRY2 pre-Messenger-RNA. Mol Cell Biol. 1995, 15: 6454-6464.PubMed CentralView ArticlePubMed
        16. Clodi E, Semrad K, Schroeder R: Assaying RNA chaperone activity in vivo using a novel RNA folding trap. EMBO J. 1999, 18: 3776-3782. 10.1093/emboj/18.13.3776.PubMed CentralView ArticlePubMed
        17. Malygin AA, Parakhnevitch NM, Ivanov AV, Eperon IC, et al: Human ribosomal protein S13 regulates expression of its own gene at the splicing step by a feedback mechanism. Nucleic Acids Res. 2007, 35: 6414-6423. 10.1093/nar/gkm701.PubMed CentralView ArticlePubMed
        18. Lindstrom MS: Emerging functions of ribosomal proteins in gene-specific transcription and translation. Biochem Biophys Res Commun. 2009, 379: 167-170. 10.1016/j.bbrc.2008.12.083.View ArticlePubMed
        19. Ebert BL, Pretz J, Bosco J, Chang CY, et al: Identification of RPS14 as a 5q(-) syndrome gene by RNA interference screen. Nature. 2008, 451: 252-253. 10.1038/451252a.View Article
        20. Yang HS, Henning D, Valdez BC: Functional interaction between RNA helicase II Gu alpha and ribosomal protein L4. FEBS J. 2005, 272: 3788-3802. 10.1111/j.1742-4658.2005.04811.x.View ArticlePubMed
        21. Jinksrobertson S, Nomura M: Ribosomal protein-S4 acts in trans as a translational repressor to regulate expression of the alpha-operon in Escherichia coli. J Bacteriol. 1982, 151: 193-202.
        22. Mattheakis LC, Nomura M: Feedback regulation of the spc operon in Escherichia coli: Translational coupling and messenger RNA processing. J Bacteriol. 1988, 170: 4484-4492.PubMed CentralPubMed
        23. Benard L, Mathy N, Grunberg-Manago M, Ehresmann B, et al: Identification in a pseudoknot of a U.G motif essential for the regulation of the expression of ribosomal protein S15. Proc Natl Acad Sci USA. 1998, 95: 2564-2567. 10.1073/pnas.95.5.2564.PubMed CentralView ArticlePubMed
        24. Mazumder B, Sampath P, Seshadri V, Maitra RK, et al: Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control. Cell. 2003, 115: 187-198. 10.1016/S0092-8674(03)00773-6.View ArticlePubMed
        25. Panagiotidis CA, Huang SC, Canellakis ES: Relationship of the expression of the S20 and L34 ribosomal proteins to polyamine biosynthesis in Escherichia coli. Int J Biochem Cell Biol. 1995, 27: 157-168. 10.1016/1357-2725(94)00068-M.View ArticlePubMed
        26. Wickner RB, Ridley SP, Fried HM, Ball SG: Ribosomal protein L3 is involved in replication or maintenance of the killer double-stranded RNA genome of Saccharomyces cerevisiae. Proc Natl Acad Sci USA. 1982, 79: 4706-4708. 10.1073/pnas.79.15.4706.PubMed CentralView ArticlePubMed
        27. Yacoub A, Augeri L, Kelley MR, Doetsch PW, et al: A Drosophila ribosomal protein contains 8-oxoguanine and abasic site DNA repair activities. EMBO J. 1996, 15: 2306-2312.PubMed CentralPubMed
        28. Hegde V, Yadavilli S, Deutsch WA: Knockdown of ribosomal protein S3 protects human cells from genotoxic stress. DNA Repair. 2007, 6: 94-99. 10.1016/j.dnarep.2006.09.004.View ArticlePubMed
        29. Yacoub A, Kelley MR, Deutsch WA: Drosophila ribosomal protein PO contains apurinic/apyrimidinic endonuclease activity. Nucleic Acids Res. 1996, 24: 4298-4303. 10.1093/nar/24.21.4298.PubMed CentralView ArticlePubMed
        30. Moorthamer M, Chaudhuri B: Identification of ribosomal protein L34 as a novel Cdk5 inhibitor. Biochem Biophys Res Commun. 1999, 255: 631-638. 10.1006/bbrc.1999.0145.View ArticlePubMed
        31. Takagi M, Absalon MJ, McLure KG, Kastan MB: Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin. Cell. 2005, 123: 49-63. 10.1016/j.cell.2005.07.034.View ArticlePubMed
        32. Neumann F, Krawinkel U: Constitutive expression of human ribosomal protein L7 arrests the cell cycle in G(1) and induces apoptosis in Jurkat T-lymphoma cells. Exp Cell Res. 1997, 230: 252-261. 10.1006/excr.1996.3417.View ArticlePubMed
        33. Chen FW, Ioannou YA: Ribosomal proteins in cell proliferation and apoptosis. Int Rev Immunol. 1999, 18: 429-448. 10.3109/08830189909088492.View ArticlePubMed
        34. Ofir-Rosenfeld Y, Boggs K, Michael D, Kastan MB, et al: Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26. Mol Cell. 2008, 32: 180-189. 10.1016/j.molcel.2008.08.031.PubMed CentralView ArticlePubMed
        35. Chen D, Zhang Z, Li M, Wang W, et al: Ribosomal protein S7 as a novel modulator of p53-MDM2 interaction: Binding to MDM2, stabilization of p53 protein, and activation of p53 function. Oncogene. 2007, 26: 5029-5037. 10.1038/sj.onc.1210327.View ArticlePubMed
        36. McGowan KA, Li JZ, Park CY, Beaudry V, et al: Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects. Nat Genet. 2008, 40: 963-970. 10.1038/ng.188.PubMed CentralView ArticlePubMed
        37. He H, Sun Y: Ribosomal protein S27L is a direct p53 target that regulates apoptosis. Oncogene. 2007, 26: 2707-2716. 10.1038/sj.onc.1210073.View ArticlePubMed
        38. Warner JR, McIntosh KB: How common are extraribosomal functions of ribosomal proteins?. Mol Cell. 2009, 34: 3-11. 10.1016/j.molcel.2009.03.006.PubMed CentralView ArticlePubMed
        39. Wang M, Hu YJ, Stearns ME: RPS2: A novel therapeutic target in prostate cancer. J Exp Clin Cancer Res. 2009, 28: 6-10.1186/1756-9966-28-6.PubMed CentralView ArticlePubMed
        40. Naora H: Involvement of ribosomal proteins in regulating cell growth and apoptosis: Translational modulation or recruitment for extra-ribosomal activity?. Immunol Cell Biol. 1999, 77: 197-205. 10.1046/j.1440-1711.1999.00816.x.View ArticlePubMed
        41. Kasai H, Nadano D, Hidaka E, Higuchi K, et al: Differential expression of ribosomal proteins in human normal and neoplastic colorectum. J Histochem Cytochem. 2003, 51: 567-573. 10.1177/002215540305100502.View ArticlePubMed
        42. Wang YX, Cheong D, Chan S, Hooi SC: Ribosomal protein L7a gene is up-regulated but not fused to the tyrosine kinase receptor as chimeric trk oncogene in human colorectal carcinoma. Int J Oncol. 2000, 16: 757-762.PubMed
        43. Zheng SE, Yao Y, Dong Y, Lin F, et al: Down-regulation of ribosomal protein L7A in human osteosarcoma. J Cancer Res Clin Oncol. 2009, 135: 1025-1031. 10.1007/s00432-008-0538-4.View ArticlePubMed
        44. Kobayashi T, Sasaki Y, Oshima Y, Yamamoto H, et al: Activation of the ribosomal protein L13 gene in human gastrointestinal cancer. Int J Mol Med. 2006, 18: 161-170.PubMed
        45. Wang Q, Yang CH, Zhou J, Wang XQ, et al: Cloning and characterization of full-length human ribosomal protein L15 cDNA which was overexpressed in esophageal cancer. Gene. 2001, 263: 205-209. 10.1016/S0378-1119(00)00570-9.View ArticlePubMed
        46. Wang H, Zhao LN, Li KZ, Ling R, et al: Overexpression of ribosomal protein L15 is associated with cell proliferation in gastric cancer. BMC Cancer. 2006, 6: 91-10.1186/1471-2407-6-91.PubMed CentralView ArticlePubMed
        47. Henry JL, Coggin DL, King CR: High-level expression of the ribosomal protein L19 in human breast tumors that overexpress Erbb-2. Cancer Res. 1993, 53: 1403-1408.PubMed
        48. Bee A, Ke YQ, Forootan S, Lin K, et al: Ribosomal protein L19 is a prognostic marker for human prostate cancer. Clin Cancer Res. 2006, 12: 2061-2065. 10.1158/1078-0432.CCR-05-2445.View ArticlePubMed
        49. Kondoh N, Shuda M, Tanaka K, Wakatsuki T, et al: Enhanced expression of S8, L12, L23a, L27 and L30 ribosomal protein mRNAs in human hepatocellular carcinoma. Anticancer Res. 2001, 21: 2429-2433.PubMed
        50. De Bortoli M, Castellino RC, Lu XY, Deyo J, et al: Medulloblastoma outcome is adversely associated with overexpression of EEF1D, RPL30, and RPS20 on the long arm of chromosome 8. BMC Cancer. 2006, 6: 223-10.1186/1471-2407-6-223.PubMed CentralView ArticlePubMed
        51. Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, et al: The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nat Genet. 1999, 21: 169-75. 10.1038/5951.View ArticlePubMed
        52. Gazda HT, Sheen MR, Vlachos A, Choesmel V, et al: Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet. 2008, 83: 769-780. 10.1016/j.ajhg.2008.11.004.PubMed CentralView ArticlePubMed
        53. Danilova N, Sakamoto KM, Lin S: Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family. Blood. 2008, 112: 5228-5237. 10.1182/blood-2008-01-132290.View ArticlePubMed
        54. Watanabe M, Zinn AR, Page DC, Nishimoto T: Functional equivalence of human X-encoded and Y-encoded isoforms of ribosomal protein-S4 consistent with a role in Turner syndrome. Nat Genet. 1993, 4: 268-271. 10.1038/ng0793-268.View ArticlePubMed
        55. Zhang WY, Hawse J, Huang QL, Sheetz N, et al: Decreased expression of ribosomal proteins in human age-related cataract. Invest Ophthalmol Vis Sci. 2002, 43: 198-204.PubMed CentralPubMed
        56. Kenmochi N, Yoshihama M, Higa S, Tanaka T: The human ribosomal protein L6 gene in a critical region for Noonan syndrome. J Hum Genet. 2000, 45: 290-293. 10.1007/s100380070018.View ArticlePubMed
        57. Oliver ER, Saunders TL, Tarle SA, Glaser T: Ribosomal protein L24 defect in belly spot and tail (Bst), a mouse Minute. Development. 2004, 131: 3907-3920. 10.1242/dev.01268.PubMed CentralView ArticlePubMed
        58. Schadt EE, Molony C, Chudin E, Hao K, et al: Mapping the genetic architecture of gene expression in human liver. PLoS Biol. 2008, 6: 1020-1032.View Article
        59. Byrne ME: A role for the ribosome in development. Trends Plant Sci. 2009, 14: 512-519. 10.1016/j.tplants.2009.06.009.View ArticlePubMed
        60. Chakraborty A, Uechi T, Higa S, Torihara H, et al: Loss of ribosomal protein L11 affects zebrafish embryonic development through a p53-dependent apoptotic response. PLoS One. 2009, 4: e4152-10.1371/journal.pone.0004152.PubMed CentralView ArticlePubMed
        61. Curran SP, Ruvkun G: Lifespan regulation by evolutionarily conserved genes essential for viability. Plos Genet. 2007, 3: e56-10.1371/journal.pgen.0030056.PubMed CentralView ArticlePubMed
        62. Murphy CT, McCarroll SA, Bargmann CI, Fraser A, et al: Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature. 2003, 424: 277-284. 10.1038/nature01789.View ArticlePubMed
        63. Canto C, Auwerx J: Caloric restriction, SIRT1 and longevity. Trends Endocrinol Metab. 2009, 20: 325-331. 10.1016/j.tem.2009.03.008.PubMed CentralView ArticlePubMed
        64. Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, et al: Genetics: Influence of TOR kinase on lifespan in C. elegans. Nature. 2003, 426: 620-View ArticlePubMed
        65. Stanfel MN, Shamieh LS, Kaeberlein M, Kennedy BK: The TOR pathway comes of age. Biochim Biophys Acta. 2009, 1790: 1067-1074. 10.1016/j.bbagen.2009.06.007.PubMed CentralView ArticlePubMed
        66. Selman C, Tullet JMA, Wieser D, Irvine E, et al: Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science. 2009, 326: 140-144. 10.1126/science.1177221.View ArticlePubMed

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