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Gene Review

ELAVL3  -  ELAV like neuron-specific RNA binding...

Homo sapiens

Synonyms: DKFZp547J036, ELAV-like protein 3, HUC, HUCL, Hu-antigen C, ...
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Disease relevance of ELAVL3

  • The PLE21/HuC neural protein is an autoantigen for anti-neuronal nuclear autoantibodies (ANNA-1/anti-Hu/Type IIa antibodies) from a patient with paraneoplastic limbic encephalomyelitis and small cell lung carcinoma [1].
  • The serum of all patients with anti-Hu-associated paraneoplastic encephalomyelitis and sensory neuronopathy react with HuD and Hel-N1, but the reactivity with HuC is unknown [2].
  • First, a partially transformed non-virus-producing cell line was obtained after infection of HUC with simian virus 40 (SV40) [3].
  • To study the role of the epithelium in the innate response to herpes simplex virus 1 (HSV-1) infection of the cornea, we used a telomerase-immortalized human corneal epithelial cell (HCEC) line, HUCL, and primary HCECs as a model and infected the cells with HSV-1 (KOS strain) [4].

High impact information on ELAVL3

  • Based on co-labeling with the pan-neuronal marker HuC/D we conclude that submucous nerve cells potentially express heteromeric 5-HT3A/B receptors [5].
  • By contrast, generic neuronal differentiation seems to be unaffected, as the expression of elavl3 (HuC) is not reduced in hands off sympathetic ganglia [6].
  • Whereas three of the Elav family members (Hel-N1, HuC, and HuD) are restricted to young and mature neurons, HuR is more broadly expressed, including proliferating cells of the developing CNS [7].
  • The deduced amino acid sequence of the RBP9 proteins is highly similar to those of three other nervous system-specific genes, human HuC and HuD and Drosophila elav, which also encode proteins with three RRMs [8].
  • RESULTS: Exposure of HUCL cells to live, but not heat-killed, S. aureus resulted in NF-kappaB activation in a time-dependent manner, as assessed by the increase in IkappaB-alpha phosphorylation and degradation [9].

Biological context of ELAVL3

  • Localization of HuC (ELAVL3) to chromosome 19p13.2 by fluorescence in situ hybridization utilizing a novel tyramide labeling technique [10].
  • Exposure of both HUCL and primary HCE cells to purified PA flagellin (250 ng/mL) resulted in IkappaB-alpha phosphorylation and degradation in a time-dependent manner [11].
  • Finally, some CC-contacting cells expressed HuC/D - a marker of immature neurones - and fired action potentials [12].
  • Toll-like receptor (TLR)-5, an innate immunity receptor for flagellin, was expressed in HUCL cells and located at the cell surface of the basal and wing, but not in superficial, cells of human corneal epithelium [11].
  • Finally, recent findings generated using in vitro transformation systems with human uroepithelial cells provide strong evidence that loss of genes on 3p, which occurs in approximately 20% of bladder cancers, and/or gain of genes on 20q play an important role in blocking HUC cellular senescence [13].

Anatomical context of ELAVL3

  • Moreover, the generation of neurons in sphere cultures induced immunoreactivity to the ELAV-like neuronal RNA-binding proteins HuC/D, which have been implicated in mechanisms of nerve cell differentiation [14].
  • Purified flagellin was used to challenge HUCL, a telomerase-immortalized HCE cell line, and primarily cultured HCE cells [11].
  • Normal human urinary tract epithelial cells (HUC) were neoplastically transformed in vitro using a step-wise strategy [3].
  • METHODS: HUCL, a telomerase-immortalized HCEC line, and primary cultures of HCECs were challenged with live or heat-killed S. aureus, its exoproducts, or cell wall components lipoteichoic acid (LTA) and peptidoglycan (PGN) [9].
  • Induction of cytotoxic T lymphocytes specific for paraneoplastic cerebellar degeneration-associated antigen in vivo by DNA immunization [15].

Associations of ELAVL3 with chemical compounds

  • Those investigated displaying potential occupational utility included the induction of ornithine decarboxylase (ODC), DNA adducts, and altered proteins, as detected on HUC two-dimensional polyacrylamide gel electrophoresis protein maps [16].

Other interactions of ELAVL3

  • HuC is a neural-specific member of the Elav family of RNA-binding proteins [10].
  • Deletions of the internal or terminal amino acid residues of the first RRM (RRM1) of the HuC/ple21 ELAV-like protein completely abolished RNA binding [17].
  • RNA-binding analyses of HuC and HuD with the VEGF and c-myc 3'-untranslated regions using a novel ELISA-based assay [18].

Analytical, diagnostic and therapeutic context of ELAVL3

  • Northern blot analysis indicated that N cells express all three Hu genes, HuD, HuC and Hel-N1 [19].
  • Fab GLN495 recognized HuD and other related proteins (HuC and Hel-N1, or Hu antigens) in immunoblots of these recombinant proteins and in immunohistochemical and Western blot analysis of SCLC and neurons [20].


  1. Antibody recognition and RNA binding of a neuronal nuclear autoantigen associated with paraneoplastic neurological syndromes and small cell lung carcinoma. Kumagai, T., Kitagawa, Y., Hirose, G., Sakai, K. J. Neuroimmunol. (1999) [Pubmed]
  2. Hu antigens: reactivity with Hu antibodies, tumor expression, and major immunogenic sites. Manley, G.T., Smitt, P.S., Dalmau, J., Posner, J.B. Ann. Neurol. (1995) [Pubmed]
  3. Neoplastic transformation of SV40-immortalized human urinary tract epithelial cells by in vitro exposure to 3-methylcholanthrene. Reznikoff, C.A., Loretz, L.J., Christian, B.J., Wu, S.Q., Meisner, L.F. Carcinogenesis (1988) [Pubmed]
  4. Herpes simplex virus 1 infection induces the expression of proinflammatory cytokines, interferons and TLR7 in human corneal epithelial cells. Li, H., Zhang, J., Kumar, A., Zheng, M., Atherton, S.S., Yu, F.S. Immunology (2006) [Pubmed]
  5. Serotonin excites neurons in the human submucous plexus via 5-HT3 receptors. Michel, K., Zeller, F., Langer, R., Nekarda, H., Kruger, D., Dover, T.J., Brady, C.A., Barnes, N.M., Schemann, M. Gastroenterology (2005) [Pubmed]
  6. The bHLH transcription factor hand2 is essential for noradrenergic differentiation of sympathetic neurons. Lucas, M.E., M??ller, F., R??diger, R., Henion, P.D., Rohrer, H. Development (2006) [Pubmed]
  7. HuR, a RNA stability factor, is expressed in malignant brain tumors and binds to adenine- and uridine-rich elements within the 3' untranslated regions of cytokine and angiogenic factor mRNAs. Nabors, L.B., Gillespie, G.Y., Harkins, L., King, P.H. Cancer Res. (2001) [Pubmed]
  8. The Drosophila gene rbp9 encodes a protein that is a member of a conserved group of putative RNA binding proteins that are nervous system-specific in both flies and humans. Kim, Y.J., Baker, B.S. J. Neurosci. (1993) [Pubmed]
  9. Innate immune response of corneal epithelial cells to Staphylococcus aureus infection: role of peptidoglycan in stimulating proinflammatory cytokine secretion. Kumar, A., Zhang, J., Yu, F.S. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  10. Localization of HuC (ELAVL3) to chromosome 19p13.2 by fluorescence in situ hybridization utilizing a novel tyramide labeling technique. Van Tine, B.A., Knops, J.F., Butler, A., Deloukas, P., Shaw, G.M., King, P.H. Genomics (1998) [Pubmed]
  11. Toll-like receptor 5-mediated corneal epithelial inflammatory responses to Pseudomonas aeruginosa flagellin. Zhang, J., Xu, K., Ambati, B., Yu, F.S. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  12. Functional and molecular clues reveal precursor-like cells and immature neurones in the turtle spinal cord. Russo, R.E., Fernández, A., Reali, C., Radmilovich, M., Trujillo-Cenóz, O. J. Physiol. (Lond.) (2004) [Pubmed]
  13. A molecular genetic model of human bladder cancer pathogenesis. Reznikoff, C.A., Belair, C.D., Yeager, T.R., Savelieva, E., Blelloch, R.H., Puthenveettil, J.A., Cuthill, S. Semin. Oncol. (1996) [Pubmed]
  14. Turning teratocarcinoma cells into neurons: rapid differentiation of NT-2 cells in floating spheres. Paquet-Durand, F., Tan, S., Bicker, G. Brain Res. Dev. Brain Res. (2003) [Pubmed]
  15. Induction of cytotoxic T lymphocytes specific for paraneoplastic cerebellar degeneration-associated antigen in vivo by DNA immunization. Sakai, K., Shirakawa, T., Kitagawa, Y., Li, Y., Hirose, G. J. Autoimmun. (2001) [Pubmed]
  16. Occupational applications of a human cancer research model. Savage, R.E., DeBord, D.G., Swaminathan, S., Butler, M.A., Snawder, J., Kanitz, M.H., Cheever, K., Reid, T., Werren, D. J. Occup. Environ. Med. (1998) [Pubmed]
  17. Analysis of the RNA recognition motifs of human neuronal ELAV-like proteins in binding to a cytokine mRNA. Sakai, K., Kitagawa, Y., Hirose, G. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  18. RNA-binding analyses of HuC and HuD with the VEGF and c-myc 3'-untranslated regions using a novel ELISA-based assay. King, P.H. Nucleic Acids Res. (2000) [Pubmed]
  19. HuD, a neuronal-specific RNA-binding protein, is a potential regulator of MYCN expression in human neuroblastoma cells. Ross, R.A., Lazarova, D.L., Manley, G.T., Smitt, P.S., Spengler, B.A., Posner, J.B., Biedler, J.L. Eur. J. Cancer (1997) [Pubmed]
  20. Selection of recombinant anti-HuD Fab fragments from a phage display antibody library of a lung cancer patient with paraneoplastic encephalomyelitis. Graus, Y.F., Verschuuren, J.J., Degenhardt, A., van Breda Vriesman, P.J., De Baets, M.H., Posner, J.B., Burton, D.R., Dalmau, J. J. Neuroimmunol. (1998) [Pubmed]
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