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Hum Genomics. 2010; 4(5): 327–344.
Published online Jun 1, 2010. doi:  10.1186/1479-7364-4-5-327
PMCID: PMC3500163
The other lives of ribosomal proteins
Rital B Bhavsar,1 Leah N Makley,1 and Panagiotis A Tsoniscorresponding author1
1Department of Biology, University of Dayton, Dayton, OH 45469-2320, USA
corresponding authorCorresponding author.
Panagiotis A Tsonis: panagiotis.tsonis/at/notes.udayton.edu
Received April 29, 2010; Accepted April 29, 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
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 (Table4)4) and S2 (Table (Table55).
Table S1
Table S1
Function and regulation of eukaryotic small subunit ribosomal proteins
Table S2
Table S2
Function and regulation of eukaryotic large subunit 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 (Table11).
Table 1
Table 1
Ribosomal proteins involved in gene regulation mechanisms
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 (Table22).
Table 2
Table 2
Ribosomal proteins in DNA repair mechanisms
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 [35-38]. 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 (Table33).
Table 3
Table 3
Expression pattern of ribosomal proteins in cancers
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 (Figure1).1). Any change in this expression profile thus affects the protein machinery that is necessary for the normal development of an organism.
Figure 1
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/ (more ...)
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
Table S3
Function and regulation of prokaryotic small subunit ribosomal proteins
Table S4
Table S4
Function and regulation of prokaryotic large subunit ribosomal proteins
  • Lodish H, Berk A, Zipursky SL, Matsudaira P, Molecular cell biology. 4. W.H. Freeman and Co., New York, NY; 2000.
  • Zimmermann RA. The double life of ribosomal proteins. Cell. 2003;115:130–132. doi: 10.1016/S0092-8674(03)00804-3. [PubMed] [Cross Ref]
  • Wool IG. Extraribosomal functions of ribosomal proteins. Trends Biochem Sci. 1996;21:164–165. [PubMed]
  • 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. doi: 10.1261/rna.1099108. [PubMed] [Cross Ref]
  • Grundy FJ, Henkin TM. The rpsd gene, encoding ribosomal-protein S4, is autogenously regulated in Bacillus subtilis. J Bacteriol. 1991;173:4595–4602. [PMC free article] [PubMed]
  • 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. doi: 10.1016/j.cell.2007.10.009. [PubMed] [Cross Ref]
  • 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. doi: 10.1016/j.molcel.2008.09.019. [PMC free article] [PubMed] [Cross Ref]
  • Mogridge J, Greenblatt J. Specific binding of Escherichia coli ribosomal protein S1 to boxA transcriptional antiterminator RNA. J Bacteriol. 1998;180:2248–2252. [PMC free article] [PubMed]
  • 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. doi: 10.1021/bi020638i. [PubMed] [Cross Ref]
  • 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. doi: 10.1093/emboj/20.14.3811. [PubMed] [Cross Ref]
  • 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. doi: 10.1073/pnas.81.12.3612. [PubMed] [Cross Ref]
  • Lai MD, Xu J. Ribosomal proteins and colorectal cancer. Curr Genomics. 2007;8:43–49. doi: 10.2174/138920207780076938. [PMC free article] [PubMed] [Cross Ref]
  • 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. doi: 10.1093/nar/gkg899. [PMC free article] [PubMed] [Cross Ref]
  • 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. doi: 10.1093/toxsci/kfj040. [PubMed] [Cross Ref]
  • 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. [PMC free article] [PubMed]
  • Clodi E, Semrad K, Schroeder R. Assaying RNA chaperone activity in vivo using a novel RNA folding trap. EMBO J. 1999;18:3776–3782. doi: 10.1093/emboj/18.13.3776. [PubMed] [Cross Ref]
  • 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. doi: 10.1093/nar/gkm701. [PMC free article] [PubMed] [Cross Ref]
  • Lindstrom MS. Emerging functions of ribosomal proteins in gene-specific transcription and translation. Biochem Biophys Res Commun. 2009;379:167–170. doi: 10.1016/j.bbrc.2008.12.083. [PubMed] [Cross Ref]
  • 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. doi: 10.1038/451252a. [PubMed] [Cross Ref]
  • Yang HS, Henning D, Valdez BC. Functional interaction between RNA helicase II Gu alpha and ribosomal protein L4. FEBS J. 2005;272:3788–3802. doi: 10.1111/j.1742-4658.2005.04811.x. [PubMed] [Cross Ref]
  • 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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. doi: 10.1073/pnas.95.5.2564. [PubMed] [Cross Ref]
  • 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. doi: 10.1016/S0092-8674(03)00773-6. [PubMed] [Cross Ref]
  • 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. doi: 10.1016/1357-2725(94)00068-M. [PubMed] [Cross Ref]
  • 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. doi: 10.1073/pnas.79.15.4706. [PubMed] [Cross Ref]
  • 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]
  • Hegde V, Yadavilli S, Deutsch WA. Knockdown of ribosomal protein S3 protects human cells from genotoxic stress. DNA Repair. 2007;6:94–99. doi: 10.1016/j.dnarep.2006.09.004. [PubMed] [Cross Ref]
  • Yacoub A, Kelley MR, Deutsch WA. Drosophila ribosomal protein PO contains apurinic/apyrimidinic endonuclease activity. Nucleic Acids Res. 1996;24:4298–4303. doi: 10.1093/nar/24.21.4298. [PMC free article] [PubMed] [Cross Ref]
  • Moorthamer M, Chaudhuri B. Identification of ribosomal protein L34 as a novel Cdk5 inhibitor. Biochem Biophys Res Commun. 1999;255:631–638. doi: 10.1006/bbrc.1999.0145. [PubMed] [Cross Ref]
  • 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. doi: 10.1016/j.cell.2005.07.034. [PubMed] [Cross Ref]
  • 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. doi: 10.1006/excr.1996.3417. [PubMed] [Cross Ref]
  • Chen FW, Ioannou YA. Ribosomal proteins in cell proliferation and apoptosis. Int Rev Immunol. 1999;18:429–448. doi: 10.3109/08830189909088492. [PubMed] [Cross Ref]
  • 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. doi: 10.1016/j.molcel.2008.08.031. [PMC free article] [PubMed] [Cross Ref]
  • 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. doi: 10.1038/sj.onc.1210327. [PubMed] [Cross Ref]
  • 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. doi: 10.1038/ng.188. [PubMed] [Cross Ref]
  • He H, Sun Y. Ribosomal protein S27L is a direct p53 target that regulates apoptosis. Oncogene. 2007;26:2707–2716. doi: 10.1038/sj.onc.1210073. [PubMed] [Cross Ref]
  • Warner JR, McIntosh KB. How common are extraribosomal functions of ribosomal proteins? Mol Cell. 2009;34:3–11. doi: 10.1016/j.molcel.2009.03.006. [PMC free article] [PubMed] [Cross Ref]
  • Wang M, Hu YJ, Stearns ME. RPS2: A novel therapeutic target in prostate cancer. J Exp Clin Cancer Res. 2009;28:6. doi: 10.1186/1756-9966-28-6. [PMC free article] [PubMed] [Cross Ref]
  • 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. doi: 10.1046/j.1440-1711.1999.00816.x. [PubMed] [Cross Ref]
  • 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. doi: 10.1177/002215540305100502. [PubMed] [Cross Ref]
  • 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]
  • 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. doi: 10.1007/s00432-008-0538-4. [PubMed] [Cross Ref]
  • 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]
  • 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. doi: 10.1016/S0378-1119(00)00570-9. [PubMed] [Cross Ref]
  • 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. doi: 10.1186/1471-2407-6-91. [PMC free article] [PubMed] [Cross Ref]
  • 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]
  • 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. doi: 10.1158/1078-0432.CCR-05-2445. [PubMed] [Cross Ref]
  • 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]
  • 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. doi: 10.1186/1471-2407-6-223. [PMC free article] [PubMed] [Cross Ref]
  • 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. doi: 10.1038/5951. [PubMed] [Cross Ref]
  • 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. doi: 10.1016/j.ajhg.2008.11.004. [PubMed] [Cross Ref]
  • 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. doi: 10.1182/blood-2008-01-132290. [PubMed] [Cross Ref]
  • 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. doi: 10.1038/ng0793-268. [PubMed] [Cross Ref]
  • 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. [PMC free article] [PubMed]
  • 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. doi: 10.1007/s100380070018. [PubMed] [Cross Ref]
  • 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. doi: 10.1242/dev.01268. [PMC free article] [PubMed] [Cross Ref]
  • 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.
  • Byrne ME. A role for the ribosome in development. Trends Plant Sci. 2009;14:512–519. doi: 10.1016/j.tplants.2009.06.009. [PubMed] [Cross Ref]
  • 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. doi: 10.1371/journal.pone.0004152. [PMC free article] [PubMed] [Cross Ref]
  • Curran SP, Ruvkun G. Lifespan regulation by evolutionarily conserved genes essential for viability. Plos Genet. 2007;3:e56. doi: 10.1371/journal.pgen.0030056. [PubMed] [Cross Ref]
  • 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. doi: 10.1038/nature01789. [PubMed] [Cross Ref]
  • Canto C, Auwerx J. Caloric restriction, SIRT1 and longevity. Trends Endocrinol Metab. 2009;20:325–331. doi: 10.1016/j.tem.2009.03.008. [PubMed] [Cross Ref]
  • 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. [PubMed]
  • Stanfel MN, Shamieh LS, Kaeberlein M, Kennedy BK. The TOR pathway comes of age. Biochim Biophys Acta. 2009;1790:1067–1074. doi: 10.1016/j.bbagen.2009.06.007. [PubMed] [Cross Ref]
  • 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. doi: 10.1126/science.1177221. [PubMed] [Cross Ref]
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