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Gene Review

UBTF  -  upstream binding transcription factor, RNA...

Homo sapiens

Synonyms: Autoantigen NOR-90, NOR-90, Nucleolar transcription factor 1, UBF, UBF-1, ...
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Disease relevance of UBTF

  • To investigate the biological significance of UBF modification, we have compared the trans-activating properties of cellular UBF and recombinant UBF expressed in Escherichia coli [1].
  • The observations of parallel responses in three different models of neonatal cardiomyocyte hypertrophy suggest that further studies on the regulation of UBF should lead to a clearer understanding of the pathways that lead to hypertrophy [2].
  • We demonstrate that the introduction of UBF antisense RNA into myocytes, using adenovirus approaches, efficiently inhibits UBF accumulation during induction of cardiomyocyte hypertrophy [3].
  • These studies expand this observation to examine directly the hypothesis that increased UBF levels are an essential requirement for the initiation of cardiac hypertrophy [3].
  • The results suggest that while anti-NOR 90 antibodies are rare, they are associated with Sjögren's syndrome in Japanese patients, and that autoimmunity is targeted toward at least 2 separate regions (amino acids 89-310 and 310-633) of the hUBF polypeptide [4].

High impact information on UBTF

  • Interestingly, we find that hUBF and xUBF form distinctly different complexes with human SL1 at both the human and Xenopus promoters [5].
  • Unexpectedly, the sequence-specific RNA pol I transcription factors hUBF and xUBF, isolated from human and Xenopus cells, respectively, recognize the same DNA sequence elements [5].
  • DNAase footprinting revealed that although SL1 alone does not bind specifically to rRNA promoter sequences, a second factor, UBF1, recruits SL1 to the template and directs binding to an extended region encompassing sequences in the UCE [6].
  • The eukaryotic upstream binding factor (UBF), recognizes the ribosomal RNA gene promoter and activates transcription mediated by RNA polymerase I through cooperative interactions with the species-specific factor, SL1 [7].
  • Expression, cellular localization and in vitro transcription studies establish that cloned hUBF encodes a nucleolar factor that binds specifically to the upstream control element and core of the rRNA gene promoter to activate transcription in a binding site-dependent manner [7].

Biological context of UBTF

  • We demonstrate that the pol I factor UBF is also inactivated by phosphorylation but recovers with different kinetics than TIF-IB/SL1 [8].
  • The results suggest that two basal transcription factors, e.g., TIF-IB/SL1 and UBF, are inactivated at mitosis and reactivated by dephosphorylation at the exit from mitosis and during G1 progression, respectively [8].
  • Recently, UBF was found distributed throughout ribosomal gene repeats rather than being restricted to promoter regions [9].
  • To directly evaluate the impact of UBF on chromatin structure, we used an in vivo assay in which UBF is targeted via a lac repressor fusion protein to a heterochromatic, amplified chromosome region containing lac operator repeats [9].
  • This observation has led to the speculation that one role of UBF binding may be to induce chromatin remodeling [9].

Anatomical context of UBTF


Associations of UBTF with chemical compounds

  • A major modification involves serine phosphoesterifications in the carboxy terminal hyperacidic tail of UBF [14].
  • Conversion of serine 388 to glycine abolishes UBF activity, whereas substitution by aspartate enhances the transactivating function of UBF [15].
  • UBF is a transcription factor that binds to the promoter of ribosomal RNA (rRNA) genes thereby supporting initiation of transcription by RNA polymerase I. Here we report that cisplatin causes a redistribution of UBF in the nucleolus of human cells, similar to that observed after inhibition of rRNA synthesis [16].
  • The clinically ineffective trans isomer (trans -DDP) does not alter the localization of either UBF or other components of the RNA polymerase I transcription machinery [16].
  • 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole treatment indicated a similar amount of UBF per transcription unit, and consequently heterogeneous size of the UBF foci can represent a variable number of transcription units per foci [17].

Physical interactions of UBTF

  • Microsequence analysis reveals that the 95-kDa TBP-binding protein is hUBF [18].
  • CAST/hPAF49 can interact with activator upstream binding factor (UBF) and, weakly, with selectivity factor 1 (SL1) at the rDNA (ribosomal DNA repeat sequence encoding the 18S, 5.8S, and 28S rRNA genes) promoter [19].
  • In vitro transcription experiments indicate that formation of the UBF1-SL1 complex is vital for transcriptional activation by UBF1 [20].
  • UBF-binding site arrays form pseudo-NORs and sequester the RNA polymerase I transcription machinery [21].

Enzymatic interactions of UBTF


Regulatory relationships of UBTF


Other interactions of UBTF

  • We show that hUBF is stably associated with TBP and is present in large TBP-containing complexes [18].
  • Upstream binding factor, UBF, is a nucleolar autoantigen involved in the transcription of ribosomal DNA genes [25].
  • Using UBF (284-670) as bait in a yeast two-hybrid screen, we have identified an interaction between UBF and TAF1, a factor involved in the transcription of cell cycle and growth regulatory genes [23].
  • Functional cooperativity between transcription factors UBF1 and SL1 mediates human ribosomal RNA synthesis [20].
  • We describe key findings for the roles of essential transcription factor SL1 and activator upstream binding factor (UBF) [26].

Analytical, diagnostic and therapeutic context of UBTF


  1. Activation of mammalian ribosomal gene transcription requires phosphorylation of the nucleolar transcription factor UBF. Voit, R., Kuhn, A., Sander, E.E., Grummt, I. Nucleic Acids Res. (1995) [Pubmed]
  2. Regulation of ribosomal DNA transcription during neonatal cardiomyocyte hypertrophy. Hannan, R.D., Rothblum, L.I. Cardiovasc. Res. (1995) [Pubmed]
  3. Increased expression of UBF is a critical determinant for rRNA synthesis and hypertrophic growth of cardiac myocytes. Brandenburger, Y., Jenkins, A., Autelitano, D.J., Hannan, R.D. FASEB J. (2001) [Pubmed]
  4. Detection of autoantibodies to nucleolar transcription factor NOR 90/hUBF in sera of patients with rheumatic diseases, by recombinant autoantigen-based assays. Fujii, T., Mimori, T., Akizuki, M. Arthritis Rheum. (1996) [Pubmed]
  5. Molecular mechanisms governing species-specific transcription of ribosomal RNA. Bell, S.P., Pikaard, C.S., Reeder, R.H., Tjian, R. Cell (1989) [Pubmed]
  6. Human rRNA transcription is modulated by the coordinate binding of two factors to an upstream control element. Learned, R.M., Learned, T.K., Haltiner, M.M., Tjian, R.T. Cell (1986) [Pubmed]
  7. Nucleolar transcription factor hUBF contains a DNA-binding motif with homology to HMG proteins. Jantzen, H.M., Admon, A., Bell, S.P., Tjian, R. Nature (1990) [Pubmed]
  8. Cell cycle-dependent regulation of RNA polymerase I transcription: the nucleolar transcription factor UBF is inactive in mitosis and early G1. Klein, J., Grummt, I. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. Upstream binding factor association induces large-scale chromatin decondensation. Chen, D., Belmont, A.S., Huang, S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  10. Specific interaction between human kinetochore protein CENP-C and a nucleolar transcriptional regulator. Pluta, A.F., Earnshaw, W.C. J. Biol. Chem. (1996) [Pubmed]
  11. MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation. Poortinga, G., Hannan, K.M., Snelling, H., Walkley, C.R., Jenkins, A., Sharkey, K., Wall, M., Brandenburger, Y., Palatsides, M., Pearson, R.B., McArthur, G.A., Hannan, R.D. EMBO J. (2004) [Pubmed]
  12. Lymphocyte mitogenic transformation is accompanied by phosphorylation of the nucleolar transcription factor UBF. Kalousek, I., Krízková, P. Cell. Mol. Biol. (Noisy-le-grand) (2000) [Pubmed]
  13. Localization of the human RNA polymerase I transcription factor gene (UBTF) to the D17S183 locus on chromosome 17q21 and construction of a long-range restriction map of the region. Jones, K.A., Black, D.M., Griffiths, B.L., Solomon, E. Genomics (1995) [Pubmed]
  14. The nucleolar transcription factor mUBF is phosphorylated by casein kinase II in the C-terminal hyperacidic tail which is essential for transactivation. Voit, R., Schnapp, A., Kuhn, A., Rosenbauer, H., Hirschmann, P., Stunnenberg, H.G., Grummt, I. EMBO J. (1992) [Pubmed]
  15. Phosphorylation of UBF at serine 388 is required for interaction with RNA polymerase I and activation of rDNA transcription. Voit, R., Grummt, I. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  16. Cisplatin inhibits synthesis of ribosomal RNA in vivo. Jordan, P., Carmo-Fonseca, M. Nucleic Acids Res. (1998) [Pubmed]
  17. Involvement of in situ conformation of ribosomal genes and selective distribution of upstream binding factor in rRNA transcription. Junéra, H.R., Masson, C., Géraud, G., Suja, J., Hernandez-Verdun, D. Mol. Biol. Cell (1997) [Pubmed]
  18. The RNA polymerase I transcription factor, upstream binding factor, interacts directly with the TATA box-binding protein. Kwon, H., Green, M.R. J. Biol. Chem. (1994) [Pubmed]
  19. RNA polymerase I-specific subunit CAST/hPAF49 has a role in the activation of transcription by upstream binding factor. Panov, K.I., Panova, T.B., Gadal, O., Nishiyama, K., Saito, T., Russell, J., Zomerdijk, J.C. Mol. Cell. Biol. (2006) [Pubmed]
  20. Functional cooperativity between transcription factors UBF1 and SL1 mediates human ribosomal RNA synthesis. Bell, S.P., Learned, R.M., Jantzen, H.M., Tjian, R. Science (1988) [Pubmed]
  21. UBF-binding site arrays form pseudo-NORs and sequester the RNA polymerase I transcription machinery. Mais, C., Wright, J.E., Prieto, J.L., Raggett, S.L., McStay, B. Genes Dev. (2005) [Pubmed]
  22. A functional screen in human cells identifies UBF2 as an RNA polymerase II transcription factor that enhances the beta-catenin signaling pathway. Grueneberg, D.A., Pablo, L., Hu, K.Q., August, P., Weng, Z., Papkoff, J. Mol. Cell. Biol. (2003) [Pubmed]
  23. The cell cycle regulatory factor TAF1 stimulates ribosomal DNA transcription by binding to the activator UBF. Lin, C.Y., Tuan, J., Scalia, P., Bui, T., Comai, L. Curr. Biol. (2002) [Pubmed]
  24. Upstream binding factor up-regulated in hepatocellular carcinoma is related to the survival and cisplatin-sensitivity of cancer cells. Huang, R., Wu, T., Xu, L., Liu, A., Ji, Y., Hu, G. FASEB J. (2002) [Pubmed]
  25. Molecular analysis of the 5' region of human ribosomal transcription factor UBF. Dühr, S., Torres-Montaner, A., Astola, A., García-Cozar, F.J., Pendón, C., Bolívar, J., Valdivia, M.M. DNA Seq. (2001) [Pubmed]
  26. TBP-TAF complex SL1 directs RNA polymerase I pre-initiation complex formation and stabilizes upstream binding factor at the rDNA promoter. Friedrich, J.K., Panov, K.I., Cabart, P., Russell, J., Zomerdijk, J.C. J. Biol. Chem. (2005) [Pubmed]
  27. Human autoantibody to RNA polymerase I transcription factor hUBF. Molecular identity of nucleolus organizer region autoantigen NOR-90 and ribosomal RNA transcription upstream binding factor. Chan, E.K., Imai, H., Hamel, J.C., Tan, E.M. J. Exp. Med. (1991) [Pubmed]
  28. Molecular cloning of the RNA polymerase I transcription factor hUBF/NOR-90 (UBTF) gene and localization to 17q21.3 by fluorescence in situ hybridization and radiation hybrid mapping. Matera, A.G., Wu, W., Imai, H., O'Keefe, C.L., Chan, E.K. Genomics (1997) [Pubmed]
  29. A step subsequent to preinitiation complex assembly at the ribosomal RNA gene promoter is rate limiting for human RNA polymerase I-dependent transcription. Panov, K.I., Friedrich, J.K., Zomerdijk, J.C. Mol. Cell. Biol. (2001) [Pubmed]
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