HuD (protein) explained

HuD otherwise known as ELAV-like protein 4 is a protein that in humans is encoded by the ELAVL4 gene.^{[1] [2]}

The HuD/ELAVL4 protein is an RNA-binding protein.^[3] HuD contains three RRM protein domains, enabling RNA binding.^[4]

HuD is expressed only in neurons and it binds to AU-rich element-containing mRNAs. As a result of this interaction the half-life of the transcript is increased. HuD is important in neurons during brain development and plasticity.^{[5] [6]}

Interactions

HuD (protein) has been shown to interact with NXF1.^[7]

Further reading

• Dalmau J, Furneaux HM, Cordon-Cardo C, Posner JB . The expression of the Hu (paraneoplastic encephalomyelitis/sensory neuronopathy) antigen in human normal and tumor tissues. . Am. J. Pathol. . 141 . 4 . 881–6 . 1992 . 1415481 . 1886624 .
• Szabo A, Dalmau J, Manley G, etal . HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal. . Cell . 67 . 2 . 325–33 . 1991 . 1655278 . 10.1016/0092-8674(91)90184-Z . 26037558 .
• Graus F, Ferrer I . Analysis of a neuronal antigen (Hu) expression in the developing rat brain detected by autoantibodies from patients with paraneoplastic encephalomyelitis. . Neurosci. Lett. . 112 . 1 . 14–8 . 1990 . 2166930 . 10.1016/0304-3940(90)90314-Y . 24113954 .
• Sekido Y, Bader SA, Carbone DP, etal . Molecular analysis of the HuD gene encoding a paraneoplastic encephalomyelitis antigen in human lung cancer cell lines. . Cancer Res. . 54 . 18 . 4988–92 . 1994 . 8069866 .
• Torà M, Graus F, de Bolòs C, Real FX . Cell surface expression of paraneoplastic encephalomyelitis/sensory neuronopathy-associated Hu antigens in small-cell lung cancers and neuroblastomas. . Neurology . 48 . 3 . 735–41 . 1997 . 9065557 . 10.1212/wnl.48.3.735. 23410604 .
• Lazarova DL, Spengler BA, Biedler JL, Ross RA . HuD, a neuronal-specific RNA-binding protein, is a putative regulator of N-myc pre-mRNA processing/stability in malignant human neuroblasts. . Oncogene . 18 . 17 . 2703–10 . 1999 . 10348344 . 10.1038/sj.onc.1202621 . 55875 .
• Park S, Myszka DG, Yu M, etal . HuD RNA recognition motifs play distinct roles in the formation of a stable complex with AU-rich RNA. . Mol. Cell. Biol. . 20 . 13 . 4765–72 . 2000 . 10848602 . 85909 . 10.1128/MCB.20.13.4765-4772.2000 .
• Wang X, Tanaka Hall TM . Structural basis for recognition of AU-rich element RNA by the HuD protein. . Nat. Struct. Biol. . 8 . 2 . 141–5 . 2001 . 11175903 . 10.1038/84131 . 12462183 .
• Beckel-Mitchener AC, Miera A, Keller R, Perrone-Bizzozero NI . Poly(A) tail length-dependent stabilization of GAP-43 mRNA by the RNA-binding protein HuD. . J. Biol. Chem. . 277 . 31 . 27996–8002 . 2002 . 12034726 . 10.1074/jbc.M201982200 . free .
• Behrends U, Jandl T, Golbeck A, etal . Novel products of the HUD, HUC, NNP-1 and alpha-internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library. . Int. J. Cancer . 100 . 6 . 669–77 . 2002 . 12209604 . 10.1002/ijc.10550 . 35369661 .
• Aronov S, Aranda G, Behar L, Ginzburg I . Visualization of translated tau protein in the axons of neuronal P19 cells and characterization of tau RNP granules. . J. Cell Sci. . 115 . Pt 19 . 3817–27 . 2003 . 12235292 . 10.1242/jcs.00058 . 16710393 .
• Angenstein F, Evans AM, Settlage RE, etal . A receptor for activated C kinase is part of messenger ribonucleoprotein complexes associated with polyA-mRNAs in neurons. . J. Neurosci. . 22 . 20 . 8827–37 . 2002 . 12388589 . 10.1523/JNEUROSCI.22-20-08827.2002. 6757688 . free .
• Deschenes-Furry J, Belanger G, Perrone-Bizzozero N, Jasmin BJ . Post-transcriptional regulation of acetylcholinesterase mRNAs in nerve growth factor-treated PC12 cells by the RNA-binding protein HuD. . J. Biol. Chem. . 278 . 8 . 5710–7 . 2003 . 12468554 . 10.1074/jbc.M209383200 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . free .
• Plonquet A, Garcia-Pons F, Fernandez E, etal . Peptides derived from the onconeural HuD protein can elicit cytotoxic responses in HHD mouse and human. . J. Neuroimmunol. . 142 . 1–2 . 93–100 . 2004 . 14512168 . 10.1016/S0165-5728(03)00269-8 . 12038485 .
• Saito K, Fujiwara T, Katahira J, etal . TAP/NXF1, the primary mRNA export receptor, specifically interacts with a neuronal RNA-binding protein HuD. . Biochem. Biophys. Res. Commun. . 321 . 2 . 291–7 . 2004 . 15358174 . 10.1016/j.bbrc.2004.06.140 .
• Rousseau A, Benyahia B, Dalmau J, etal . T cell response to Hu-D peptides in patients with anti-Hu syndrome. . J. Neurooncol. . 71 . 3 . 231–6 . 2005 . 15735910 . 2586925 . 10.1007/s11060-004-1723-1 .
• Noureddine MA, Qin XJ, Oliveira SA, etal . Association between the neuron-specific RNA-binding protein ELAVL4 and Parkinson disease. . Hum. Genet. . 117 . 1 . 27–33 . 2005 . 15827745 . 10.1007/s00439-005-1259-2 . 22359866 .
• Rual JF, Venkatesan K, Hao T, etal . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .

Notes and References

1. Muresu R, Baldini A, Gress T, Posner JB, Furneaux HM, Siniscalco M . Mapping of the gene coding for a paraneoplastic encephalomyelitis antigen (HuD) to human chromosome site 1p34 . Cytogenet Cell Genet . 65 . 3 . 177–8 . Dec 1993 . 8222755 . 10.1159/000133626 .
2. Web site: Entrez Gene: ELAVL4 ELAV (embryonic lethal, abnormal vision, Drosophila)-like 4 (Hu antigen D).
3. Szabo A, Dalmau J, Manley G, etal . HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal. . Cell . 67 . 2 . 325–33 . 1991 . 1655278 . 10.1016/0092-8674(91)90184-Z . 26037558 .
4. 2008-08-01. RNA-binding proteins in human genetic disease. Trends in Genetics. en. 24. 8. 416–425. 10.1016/j.tig.2008.05.004. 18597886. 0168-9525. Lukong. Kiven E.. Chang. Kai-wei. Khandjian. Edouard W.. Richard. Stéphane.
5. Nora Perrone-Bizzozero . Federico Bolognani . Role of HuD and other RNA-binding proteins in neural development and plasticity . J Neurosci Res . 68 . 2 . 121–126 . 2002 . 11948657 . 10.1002/jnr.10175. free .
6. Federico Bolognani . Nora Perrone-Bizzozero . RNA-protein interactions and control of mRNA stability in neurons . J Neurosci Res . 86 . 3 . 481–489 . 2008 . 17853436 . 10.1002/jnr.21473. 27076039 .
7. Saito . Kuniaki . Fujiwara Toshinobu . Katahira Jun . Inoue Kunio . Sakamoto Hiroshi . Aug 2004 . TAP/NXF1, the primary mRNA export receptor, specifically interacts with a neuronal RNA-binding protein HuD . Biochem. Biophys. Res. Commun. . 321 . 2 . 291–7 . United States. 0006-291X. 15358174 . 10.1016/j.bbrc.2004.06.140 .