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Gene Review

RPL4  -  ribosomal protein L4

Homo sapiens

Synonyms: 60S ribosomal protein L1, 60S ribosomal protein L4, L4, RPL1
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Disease relevance of RPL4

  • A number of clinical studies have implicated the cell adhesion molecule L1 in Hirschsprung's disease [1].
  • Moreover, it contributes to knowledge of the structure of HPV-16 L1 VLPs and their derivatives [2].
  • Identification of two cross-neutralizing linear epitopes within the L1 major capsid protein of human papillomaviruses [3].
  • HPV-11 L1 VLPs could also be dissociated by treatment with carbonate buffer at pH 9.6, but VLPs could not be regenerated following carbonate treatment [4].
  • We also show that plant-expressed L1 self-assembles into VLPs with immunological properties comparable to those of native HPV virions [5].

Psychiatry related information on RPL4

  • Mutations in L1CAM, the gene encoding the transmembrane multifunctional neuronal adhesion molecule L1, are associated with neurodevelopmental disorders including X-linked hydrocephalus and mental retardation [6].

High impact information on RPL4

  • The LINE-1 (L1) retrotransposon, the most important human mobile element, shapes the genome in many ways [7].
  • RESULTS: We show that L1 is expressed by neural crest cells as they colonize the gut [1].
  • L1-deficient mice show a small but significant reduction in neural crest cell migration at early developmental stages, but the entire gastrointestinal tract is colonized [1].
  • We show here that L1-EGFP can undergo retrotransposition in vivo and produce fluorescence in mouse testis [8].
  • Expression of GFP occurs only if L1-EGFP has undergone a cycle of transcription, reverse transcription, and integration into a transcriptionally permissive genomic region [8].

Chemical compound and disease context of RPL4


Biological context of RPL4

  • The deduced amino acid sequence shows that human ribosomal protein L4 has 425 amino acid residues and a calculated molecular mass of 47,821 Da [13].
  • To determine the frequency of L1-mediated transduction in the human genome, we selected 66 previously uncharacterized L1 sequences from the GenBank database [14].
  • Active LINE-1 (L1) elements possess the ability to transduce non-L1 DNA flanking their 3' ends to new genomic locations [14].
  • Taken together, these observations indicate that inhibition of p27(KIP1) transcription through PI3K-induced FKHR-L1 phosphorylation provides a novel mechanism of regulating cytokine-mediated survival and proliferation [15].
  • Occasionally, the 3' end processing machinery may bypass the L1 polyadenylation signal and instead utilize a second downstream polyadenylation site [14].

Anatomical context of RPL4

  • Here we show that in mammalian cells, Gu(alpha) physically interacts with ribosomal protein L4 (RPL4), a component of 60S ribosome large subunit [16].
  • Translational control of ribosomal protein L4 mRNA is required for rapid neurite regeneration [17].
  • This mRNA, which encodes the ribosomal protein L4, is translationally regulated during neurite regeneration in PC12 cells [17].
  • We have generated Ba/F3 cell lines expressing a tamoxifen-inducible active FKHR-L1 mutant [FKHR-L1(A3):ER*] [15].
  • It is the founder of a neural group of related cell surface receptors that share with L1 a highly conserved cytoplasmic domain that associates with the cytoskeleton [18].

Associations of RPL4 with chemical compounds

  • Importantly, ingestion of transgenic L1 potato was associated with activation of an anti-VLP immune response in mice that was qualitatively similar to that induced by VLP parenteral administration, and this response was enhanced significantly by subsequent oral boosting with purified insect cell-derived VLPs [5].
  • Finally, we found that the resistant strain harbored a 27-bp insertion in the highly conserved region of the gene encoding the ribosomal protein L4; this insertion may explain the existence of the resistance to erythromycin [19].
  • Among the 31 strains studied that showed high-level resistance to both azithromycin and clarithromycin, 28 had ribosomal alterations, 7 had mutations in ribosomal protein L4, 11 had mutations in L22, 2 had mutations in 23S rRNA, 8 had multiple mutations, and 3 had no mutations [20].
  • L1, beta1 integrin, and cadherins mediate axonal regeneration in the embryonic spinal cord [21].
  • L1 RNA, but not protein, was detected biochemically in C3 cells [22].

Other interactions of RPL4

  • If special attention to intraepithelial lesions is appropriate, RPL4 and PGK1 are recommended as the best combination of two genes [23].
  • This nuclear wheat RPL5 acquired its targeting information by duplication of an existing targeting presequence for another mitochondrial protein, ribosomal protein L4 [24].
  • Among the differentially expressed cDNAs, homologies of 96% and 87%, respectively, were found to the human proto-oncogene PTI-1 and the human ribosomal protein L4 [25].

Analytical, diagnostic and therapeutic context of RPL4

  • Based on UV crosslinking and electrophoretic mobility-shift assays using purified components, we demonstrate here that the ORF1 protein encoded by mouse L1 binds nucleic acids with a strong preference for RNA and other single-stranded nucleic acids [26].
  • L1 exon shuffling potential has been reported in cell culture assays, and two potential L1-mediated exon shuffling events have been identified in the genome [27].
  • PCR analysis of human/rodent hybrid cell line DNA samples showed that the polymorphic L1 elements were located on several different chromosomes [28].
  • Transgenic plants expressing the HPV major capsid protein L1 could be a system to produce virus-like particles for prophylactic vaccination or could even be used as edible vaccines to induce an L1-specific prophylactic immune response [29].
  • However, Northern blot analysis revealed that most of the L1 transcripts were degraded [29].


  1. The cell adhesion molecule l1 is required for chain migration of neural crest cells in the developing mouse gut. Anderson, R.B., Turner, K.N., Nikonenko, A.G., Hemperly, J., Schachner, M., Young, H.M. Gastroenterology (2006) [Pubmed]
  2. Chimeric human papillomavirus type 16 (HPV-16) L1 particles presenting the common neutralizing epitope for the L2 minor capsid protein of HPV-6 and HPV-16. Varsani, A., Williamson, A.L., de Villiers, D., Becker, I., Christensen, N.D., Rybicki, E.P. J. Virol. (2003) [Pubmed]
  3. Identification of two cross-neutralizing linear epitopes within the L1 major capsid protein of human papillomaviruses. Combita, A.L., Touzé, A., Bousarghin, L., Christensen, N.D., Coursaget, P. J. Virol. (2002) [Pubmed]
  4. Quantitative disassembly and reassembly of human papillomavirus type 11 viruslike particles in vitro. McCarthy, M.P., White, W.I., Palmer-Hill, F., Koenig, S., Suzich, J.A. J. Virol. (1998) [Pubmed]
  5. Oral immunogenicity of human papillomavirus-like particles expressed in potato. Warzecha, H., Mason, H.S., Lane, C., Tryggvesson, A., Rybicki, E., Williamson, A.L., Clements, J.D., Rose, R.C. J. Virol. (2003) [Pubmed]
  6. Missense mutations in the extracellular domain of the human neural cell adhesion molecule L1 reduce neurite outgrowth of murine cerebellar neurons. Michelson, P., Hartwig, C., Schachner, M., Gal, A., Veske, A., Finckh, U. Hum. Mutat. (2002) [Pubmed]
  7. LINE drive. retrotransposition and genome instability. Kazazian, H.H., Goodier, J.L. Cell (2002) [Pubmed]
  8. Tracking an embryonic L1 retrotransposition event. Prak, E.T., Dodson, A.W., Farkash, E.A., Kazazian, H.H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  9. Novel mechanism of resistance to oxazolidinones, macrolides, and chloramphenicol in ribosomal protein L4 of the pneumococcus. Wolter, N., Smith, A.M., Farrell, D.J., Schaffner, W., Moore, M., Whitney, C.G., Jorgensen, J.H., Klugman, K.P. Antimicrob. Agents Chemother. (2005) [Pubmed]
  10. Increased antibody responses to human papillomavirus type 16 L1 protein expressed by recombinant vaccinia virus lacking serine protease inhibitor genes. Zhou, J., Crawford, L., McLean, L., Sun, X.Y., Stanley, M., Almond, N., Smith, G.L. J. Gen. Virol. (1990) [Pubmed]
  11. Production of human papillomavirus type 16 L1 virus-like particles by recombinant Lactobacillus casei cells. Aires, K.A., Cianciarullo, A.M., Carneiro, S.M., Villa, L.L., Boccardo, E., Pérez-Martinez, G., Perez-Arellano, I., Oliveira, M.L., Ho, P.L. Appl. Environ. Microbiol. (2006) [Pubmed]
  12. HPV antibody detection by ELISA with capsid protein L1 fused to glutathione S-transferase. Sehr, P., Müller, M., Höpfl, R., Widschwendter, A., Pawlita, M. J. Virol. Methods (2002) [Pubmed]
  13. Human ribosomal protein L4: cloning and sequencing of the cDNA and primary structure of the protein. Bagni, C., Mariottini, P., Annesi, F., Amaldi, F. Biochim. Biophys. Acta (1993) [Pubmed]
  14. Transduction of 3'-flanking sequences is common in L1 retrotransposition. Goodier, J.L., Ostertag, E.M., Kazazian, H.H. Hum. Mol. Genet. (2000) [Pubmed]
  15. Forkhead transcription factor FKHR-L1 modulates cytokine-dependent transcriptional regulation of p27(KIP1). Dijkers, P.F., Medema, R.H., Pals, C., Banerji, L., Thomas, N.S., Lam, E.W., Burgering, B.M., Raaijmakers, J.A., Lammers, J.W., Koenderman, L., Coffer, P.J. Mol. Cell. Biol. (2000) [Pubmed]
  16. Functional interaction between RNA helicase II/Gu(alpha) and ribosomal protein L4. Yang, H., Henning, D., Valdez, B.C. FEBS J. (2005) [Pubmed]
  17. Translational control of ribosomal protein L4 mRNA is required for rapid neurite regeneration. Twiss, J.L., Smith, D.S., Chang, B., Shooter, E.M. Neurobiol. Dis. (2000) [Pubmed]
  18. Neural cell recognition molecule L1: from cell biology to human hereditary brain malformations. Brümmendorf, T., Kenwrick, S., Rathjen, F.G. Curr. Opin. Neurobiol. (1998) [Pubmed]
  19. Antiangiogenic effect of erythromycin: an in vitro model of Bartonella quintana infection. Meghari, S., Rolain, J.M., Grau, G.E., Platt, E., Barrassi, L., Mege, J.L., Raoult, D. J. Infect. Dis. (2006) [Pubmed]
  20. Effects of an efflux mechanism and ribosomal mutations on macrolide susceptibility of Haemophilus influenzae clinical isolates. Peric, M., Bozdogan, B., Jacobs, M.R., Appelbaum, P.C. Antimicrob. Agents Chemother. (2003) [Pubmed]
  21. L1, beta1 integrin, and cadherins mediate axonal regeneration in the embryonic spinal cord. Blackmore, M., Letourneau, P.C. J. Neurobiol. (2006) [Pubmed]
  22. L1-specific protection from tumor challenge elicited by HPV16 virus-like particles. De Bruijn, M.L., Greenstone, H.L., Vermeulen, H., Melief, C.J., Lowy, D.R., Schiller, J.T., Kast, W.M. Virology (1998) [Pubmed]
  23. DNA and RNA references for qRT-PCR assays in exfoliated cervical cells. Steinau, M., Rajeevan, M.S., Unger, E.R. The Journal of molecular diagnostics : JMD. (2006) [Pubmed]
  24. Transfer of RPS14 and RPL5 from the mitochondrion to the nucleus in grasses. Sandoval, P., León, G., Gómez, I., Carmona, R., Figueroa, P., Holuigue, L., Araya, A., Jordana, X. Gene (2004) [Pubmed]
  25. Overexpression of ribosomal proteins L4 and L5 and the putative alternative elongation factor PTI-1 in the doxorubicin resistant human colon cancer cell line LoVoDxR. Bertram, J., Palfner, K., Hiddemann, W., Kneba, M. Eur. J. Cancer (1998) [Pubmed]
  26. In vitro properties of the first ORF protein from mouse LINE-1 support its role in ribonucleoprotein particle formation during retrotransposition. Kolosha, V.O., Martin, S.L. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  27. From the Cover: Eukaryotic Transposable Elements and Genome Evolution Special Feature: Emergence of primate genes by retrotransposon-mediated sequence transduction. Xing, J., Wang, H., Belancio, V.P., Cordaux, R., Deininger, P.L., Batzer, M.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  28. Reading between the LINEs: human genomic variation induced by LINE-1 retrotransposition. Sheen, F.M., Sherry, S.T., Risch, G.M., Robichaux, M., Nasidze, I., Stoneking, M., Batzer, M.A., Swergold, G.D. Genome Res. (2000) [Pubmed]
  29. Production of human papillomavirus type 16 virus-like particles in transgenic plants. Biemelt, S., Sonnewald, U., Galmbacher, P., Willmitzer, L., Müller, M. J. Virol. (2003) [Pubmed]
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