The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

HNRNPD  -  heterogeneous nuclear ribonucleoprotein D...

Homo sapiens

Synonyms: AU-rich element RNA-binding protein 1, AUF1, AUF1A, HNRPD, Heterogeneous nuclear ribonucleoprotein D0, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of HNRPD

  • Together, these data suggest a mechanism whereby reduced cytoplasmic levels of AUF1 in MNT1 melanoma cells may lead to IL-10 overexpression, with deleterious consequences for tumor surveillance and rejection [1].
  • The AUF1 modifications as a result of uremia were reversed by treatment with R-568 to those of normal rats [2].
  • In the present study, we demonstrate a strong correlation between increased cytoplasmic expression of both AUF1 and HuR with urethane-induced neoplasia and with butylated hydroxytoluene-induced compensatory hyperplasia in mouse lung tissue [3].
  • We discuss: (a) the types of 3'-UTR sequences involved in mRNA stability, (b) AUF1, HuR and other proteins that bind to these sequences to either stabilize or destabilize the target mRNAs, and (c) the potential role of the 3'-UTR mediated mRNA stability in heart failure, myocardial infarction and hypertension [4].
  • Conduction to the parietal cortex (T12-P37 interpeak latency) worsened in both the symptomatic men and the boys with preclinical adrenomyeloneuropathy [5].

High impact information on HNRPD

  • Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs [6].
  • We show that AUF1 normally functions to protect against the lethal progression of endotoxemia [6].
  • Analysis of both endogenous and chimeric GADD45alpha mRNA revealed that in untreated cells AUF1 strongly reduced GADD45alpha mRNA stability, whereas TIAR potently inhibited GADD45alpha translation [7].
  • Here, two RNA binding proteins, the mRNA decay-promoting AUF1 and the translational suppressor TIAR, were found to interact specifically with the 3' untranslated region (UTR) of the GADD45alpha mRNA in HeLa cells [7].
  • After genotoxic stress, AUF1 and TIAR dissociated from the GADD45alpha mRNA, thereby allowing coordinated elevations in both GADD45alpha mRNA half-life and translation rate, respectively [7].

Chemical compound and disease context of HNRPD


Biological context of HNRPD


Anatomical context of HNRPD

  • There is no PT cell line, but in HEK 293 cells the 63-nt element is recognized as an instability element, and RNA interference for AUF1 decreased human PTH secretion in cotransfection experiments [13].
  • Finally, we find that the ARE-binding protein AUF1 comprises the major ARE-binding activity in cytoplasmic extracts of normal melanocytes [1].
  • AUF1 protein, a negative regulator of ARE mRNA stability, displayed strong expression in thymus and spleen cells within lymphocytic cells, moderate expression in the epithelial linings of lungs, gonadal tissues, and nuclei of most neurons in the brain, and little expression in the other tissues [14].
  • Tristetraprolin, a negative regulator of ARE mRNA stability, displayed a largely non-overlapping tissue distribution with AUF1 and was predominantly expressed in the liver and testis [14].
  • Previous genomic cloning combined with FISH and Southern analyses of a panel of monochromosomal mouse/human or hamster/human somatic cell hybrids localized two AUF1 loci to human 4q21.1-q21.2 and Xq12 (B. Wagner et al., 1996, Genomics 34: 219-222) [15].

Associations of HNRPD with chemical compounds

  • In contrast, the interaction of AUF1 with the ATF3 mRNA is decreased in histidine-deprived cells relative to control cells [12].
  • Lactate dehydrogenase is an AU-rich element-binding protein that directly interacts with AUF1 [16].
  • A "liaison dangereuse" between AUF1/hnRNPD and the oncogenic tyrosine kinase NPM-ALK [17].
  • Interaction of RNA binding proteins, such as the cloned adenosine + uridine-rich element, binding factor, AUF1, with eight AUUUA motifs in the human GM-CSF mRNA 3'-untranslated region (GM-3'-UTR) has been implicated in regulating transcript stability [18].
  • This site appears to involve a series of amino acids immediately after the third cysteine residue beginning with P37 [19].

Physical interactions of HNRPD

  • Thus, AUF1 binds to multiple destabilizing elements within the 3'-UTR that participate in the rapid turnover of the PEPCK mRNA [20].
  • The effect of the calcimimetic on PTH gene expression was posttranscriptional and correlated with differences in protein-RNA binding and posttranslational modifications of the trans acting factor AUF1 in the PT [2].
  • We demonstrate that all four AUF1 protein isoforms bind directly and strongly to initiation factor eIF4G at a C-terminal site regardless of AUF1 interaction with the ARE [21].
  • As judged by RNA-gel mobility shift assays, this rapid degradation of SH2D1A mRNA was due to a balance in binding of the factors AUF1 and HuR to its 3' UTR [22].
  • We focus initially on the basic concepts in mRNA stability with the trans-acting factors AUF1 (destabilizing) and HuR (stabilizing) [23].

Regulatory relationships of HNRPD


Other interactions of HNRPD

  • Amino acid limitation caused a slightly elevated mRNA level for HuR and AUF1 mRNA [12].
  • Increased interleukin-10 mRNA stability in melanoma cells is associated with decreased levels of A + U-rich element binding factor AUF1 [1].
  • A nuclear matrix-associated factor, SAF-B, interacts with specific isoforms of AUF1/hnRNP D [25].
  • These modifications in AUF1 correlate with changes in protein-PTH mRNA binding and PTH mRNA levels [2].
  • Based on these and other data, we propose a model for the molecular interactions of AUF1 that involves translation-dependent displacement of AUF1-PABP complexes from ARE-mRNAs with possible unmasking of the poly(A) tail [21].
  • The AUF1 effect on iNOS expression is dependent on the iNOS 3'-untranslated region sequence, as demonstrated in transfection experiments with a reporter mRNA [26].

Analytical, diagnostic and therapeutic context of HNRPD


  1. Increased interleukin-10 mRNA stability in melanoma cells is associated with decreased levels of A + U-rich element binding factor AUF1. Brewer, G., Saccani, S., Sarkar, S., Lewis, A., Pestka, S. J. Interferon Cytokine Res. (2003) [Pubmed]
  2. Increased parathyroid hormone gene expression in secondary hyperparathyroidism of experimental uremia is reversed by calcimimetics: correlation with posttranslational modification of the trans acting factor AUF1. Levi, R., Ben-Dov, I.Z., Lavi-Moshayoff, V., Dinur, M., Martin, D., Naveh-Many, T., Silver, J. J. Am. Soc. Nephrol. (2006) [Pubmed]
  3. Differential expression and localization of the mRNA binding proteins, AU-rich element mRNA binding protein (AUF1) and Hu antigen R (HuR), in neoplastic lung tissue. Blaxall, B.C., Dwyer-Nield, L.D., Bauer, A.K., Bohlmeyer, T.J., Malkinson, A.M., Port, J.D. Mol. Carcinog. (2000) [Pubmed]
  4. The role of 3'-untranslated region (3'-UTR) mediated mRNA stability in cardiovascular pathophysiology. Misquitta, C.M., Iyer, V.R., Werstiuk, E.S., Grover, A.K. Mol. Cell. Biochem. (2001) [Pubmed]
  5. A two-year trial of oleic and erucic acids ("Lorenzo's oil") as treatment for adrenomyeloneuropathy. Aubourg, P., Adamsbaum, C., Lavallard-Rousseau, M.C., Rocchiccioli, F., Cartier, N., Jambaqué, I., Jakobezak, C., Lemaitre, A., Boureau, F., Wolf, C. N. Engl. J. Med. (1993) [Pubmed]
  6. Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Lu, J.Y., Sadri, N., Schneider, R.J. Genes Dev. (2006) [Pubmed]
  7. Posttranscriptional derepression of GADD45alpha by genotoxic stress. Lal, A., Abdelmohsen, K., Pullmann, R., Kawai, T., Galban, S., Yang, X., Brewer, G., Gorospe, M. Mol. Cell (2006) [Pubmed]
  8. Regulation of the Epstein-Barr virus C promoter by AUF1 and the cyclic AMP/protein kinase A signaling pathway. Fuentes-Pananá, E.M., Peng, R., Brewer, G., Tan, J., Ling, P.D. J. Virol. (2000) [Pubmed]
  9. Vitamin B12 deficiency: a clinical and electrophysiological profile. Puri, V., Chaudhry, N., Goel, S., Gulati, P., Nehru, R., Chowdhury, D. Electromyography and clinical neurophysiology. (2005) [Pubmed]
  10. AUF1, the regulator of tumor necrosis factor alpha messenger RNA decay, is targeted by autoantibodies of patients with systemic rheumatic diseases. Skriner, K., Hueber, W., Süleymanoglu, E., Höfler, E., Krenn, V., Smolen, J., Steiner, G. Arthritis Rheum. (2008) [Pubmed]
  11. The human HNRPD locus maps to 4q21 and encodes a highly conserved protein. Dempsey, L.A., Li, M.J., DePace, A., Bray-Ward, P., Maizels, N. Genomics (1998) [Pubmed]
  12. Interaction of RNA-binding proteins HuR and AUF1 with the human ATF3 mRNA 3'-untranslated region regulates its amino acid limitation-induced stabilization. Pan, Y.X., Chen, H., Kilberg, M.S. J. Biol. Chem. (2005) [Pubmed]
  13. The protein phosphatase calcineurin determines basal parathyroid hormone gene expression. Bell, O., Gaberman, E., Kilav, R., Levi, R., Cox, K.B., Molkentin, J.D., Silver, J., Naveh-Many, T. Mol. Endocrinol. (2005) [Pubmed]
  14. Tissue distribution of AU-rich mRNA-binding proteins involved in regulation of mRNA decay. Lu, J.Y., Schneider, R.J. J. Biol. Chem. (2004) [Pubmed]
  15. Structure and genomic organization of the human AUF1 gene: alternative pre-mRNA splicing generates four protein isoforms. Wagner, B.J., DeMaria, C.T., Sun, Y., Wilson, G.M., Brewer, G. Genomics (1998) [Pubmed]
  16. Lactate dehydrogenase is an AU-rich element-binding protein that directly interacts with AUF1. Pioli, P.A., Hamilton, B.J., Connolly, J.E., Brewer, G., Rigby, W.F. J. Biol. Chem. (2002) [Pubmed]
  17. A "liaison dangereuse" between AUF1/hnRNPD and the oncogenic tyrosine kinase NPM-ALK. Fawal, M., Armstrong, F., Ollier, S., Dupont, H., Touriol, C., Monsarrat, B., Delsol, G., Payrastre, B., Morello, D. Blood (2006) [Pubmed]
  18. Increased granulocyte-macrophage colony-stimulating factor mRNA instability in cord versus adult mononuclear cells is translation-dependent and associated with increased levels of A + U-rich element binding factor. Buzby, J.S., Lee, S.M., Van Winkle, P., DeMaria, C.T., Brewer, G., Cairo, M.S. Blood (1996) [Pubmed]
  19. Defining an antigenic epitope on platelet factor 4 associated with heparin-induced thrombocytopenia. Ziporen, L., Li, Z.Q., Park, K.S., Sabnekar, P., Liu, W.Y., Arepally, G., Shoenfeld, Y., Kieber-Emmons, T., Cines, D.B., Poncz, M. Blood (1998) [Pubmed]
  20. 3'-Untranslated region of phosphoenolpyruvate carboxykinase mRNA contains multiple instability elements that bind AUF1. Hajarnis, S., Schroeder, J.M., Curthoys, N.P. J. Biol. Chem. (2005) [Pubmed]
  21. Assembly of AUF1 with eIF4G-poly(A) binding protein complex suggests a translation function in AU-rich mRNA decay. Lu, J.Y., Bergman, N., Sadri, N., Schneider, R.J. RNA (2006) [Pubmed]
  22. Expression of the SH2D1A gene is regulated by a combination of transcriptional and post-transcriptional mechanisms. Okamoto, S., Ji, H., Howie, D., Clarke, K., Gullo, C., Manning, S., Coyle, A.J., Terhorst, C. Eur. J. Immunol. (2004) [Pubmed]
  23. Control of protein expression through mRNA stability in calcium signalling. Misquitta, C.M., Chen, T., Grover, A.K. Cell Calcium (2006) [Pubmed]
  24. NMDA induces post-transcriptional regulation of {alpha}2-guanylyl-cyclase-subunit expression in cerebellar granule cells. Jurado, S., Rodríguez-Pascual, F., Sánchez-Prieto, J., Reimunde, F.M., Lamas, S., Torres, M. J. Cell. Sci. (2006) [Pubmed]
  25. A nuclear matrix-associated factor, SAF-B, interacts with specific isoforms of AUF1/hnRNP D. Arao, Y., Kuriyama, R., Kayama, F., Kato, S. Arch. Biochem. Biophys. (2000) [Pubmed]
  26. Similar regulation of human inducible nitric-oxide synthase expression by different isoforms of the RNA-binding protein AUF1. Pautz, A., Linker, K., Altenhöfer, S., Heil, S., Schmidt, N., Art, J., Knauer, S., Stauber, R., Sadri, N., Pont, A., Schneider, R.J., Kleinert, H. J. Biol. Chem. (2009) [Pubmed]
  27. Localization and physical mapping of genes encoding the A+U-rich element RNA-binding protein AUF1 to human chromosomes 4 and X. Wagner, B.J., Long, L., Rao, P.N., Pettenati, M.J., Brewer, G. Genomics (1996) [Pubmed]
  28. Tibial somatosensory evoked potential intraoperative monitoring: recommendations based on signal to noise ratio analysis of popliteal fossa, optimized P37, standard P37, and P31 potentials. MacDonald, D.B., Al Zayed, Z., Stigsby, B. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. (2005) [Pubmed]
  29. Assembly of the alpha-globin mRNA stability complex reflects binary interaction between the pyrimidine-rich 3' untranslated region determinant and poly(C) binding protein alphaCP. Chkheidze, A.N., Lyakhov, D.L., Makeyev, A.V., Morales, J., Kong, J., Liebhaber, S.A. Mol. Cell. Biol. (1999) [Pubmed]
WikiGenes - Universities