pol1 transcription initiation complex proteins


Summary: Factors that form a preinitiation complex at promoters that are specifically transcribed by RNA POLYMERASE I.

Top Publications

  1. Sheng Z, Liang Y, Lin C, Comai L, Chirico W. Direct regulation of rRNA transcription by fibroblast growth factor 2. Mol Cell Biol. 2005;25:9419-26 pubmed
    ..The 18-kDa FGF-2 localizes to rRNA genes and is necessary for the full activation of pre-rRNA synthesis in vivo. Our results demonstrate that 18-kDa FGF-2 directly regulates rRNA transcription. ..
  2. Voit R, Kuhn A, Sander E, Grummt I. Activation of mammalian ribosomal gene transcription requires phosphorylation of the nucleolar transcription factor UBF. Nucleic Acids Res. 1995;23:2593-9 pubmed
    ..The marked differences in the tryptic peptide maps of UBF from growing and serum-starved cells suggest that alterations in the degree of UBF phosphorylation may modulate rRNA synthetic activity in response to extracellular signals. ..
  3. Stefanovsky V, Moss T. The splice variants of UBF differentially regulate RNA polymerase I transcription elongation in response to ERK phosphorylation. Nucleic Acids Res. 2008;36:5093-101 pubmed publisher
    ..Thus, UBF2 functionally simulates a hemi-phosphorylated UBF whose expression may provide a means by which to tune the response of the ribosomal RNA genes to growth factor stimulation. ..
  4. Chen D, Huang S. Nucleolar components involved in ribosome biogenesis cycle between the nucleolus and nucleoplasm in interphase cells. J Cell Biol. 2001;153:169-76 pubmed
  5. Panov K, Friedrich J, Zomerdijk J. A step subsequent to preinitiation complex assembly at the ribosomal RNA gene promoter is rate limiting for human RNA polymerase I-dependent transcription. Mol Cell Biol. 2001;21:2641-9 pubmed
    ..This rate-limiting step in Pol I transcription is likely to be a major target in the regulation of rRNA gene expression. ..
  6. Laferté A, Favry E, Sentenac A, Riva M, Carles C, Chédin S. The transcriptional activity of RNA polymerase I is a key determinant for the level of all ribosome components. Genes Dev. 2006;20:2030-40 pubmed
  7. Chen D, Belmont A, Huang S. Upstream binding factor association induces large-scale chromatin decondensation. Proc Natl Acad Sci U S A. 2004;101:15106-11 pubmed
    ..These studies also provide an in vivo model simulating ribosomal DNA transactivation outside the nucleolus, allowing temporal and spatial analyses of chromatin remodeling and assembly of the pol I transcription machinery. ..
  8. Halkidou K, Logan I, Cook S, Neal D, Robson C. Putative involvement of the histone acetyltransferase Tip60 in ribosomal gene transcription. Nucleic Acids Res. 2004;32:1654-65 pubmed
    ..The present study underlines the importance of acetylation in rDNA transcription and directly implicates Tip60 in the process of ribosomal gene transcription. ..
  9. Mayer C, Bierhoff H, Grummt I. The nucleolus as a stress sensor: JNK2 inactivates the transcription factor TIF-IA and down-regulates rRNA synthesis. Genes Dev. 2005;19:933-41 pubmed
    ..Our data identify TIF-IA as a downstream target of the JNK pathway and suggest a critical role of JNK2 to protect rRNA synthesis against the harmful consequences of cellular stress. ..

More Information


  1. Stefanovsky V, Langlois F, Gagnon Kugler T, Rothblum L, Moss T. Growth factor signaling regulates elongation of RNA polymerase I transcription in mammals via UBF phosphorylation and r-chromatin remodeling. Mol Cell. 2006;21:629-39 pubmed
    ..The data suggest a mechanism for coordinating the cotranscriptional assembly of preribosomal particles. ..
  2. Meraner J, Lechner M, Loidl A, Goralik Schramel M, Voit R, Grummt I, et al. Acetylation of UBF changes during the cell cycle and regulates the interaction of UBF with RNA polymerase I. Nucleic Acids Res. 2006;34:1798-806 pubmed
    ..The results suggest that acetylation and deacetylation of UBF regulate rRNA synthesis during cell cycle progression. ..
  3. Hirschler Laszkiewicz I, Cavanaugh A, Hu Q, Catania J, Avantaggiati M, Rothblum L. The role of acetylation in rDNA transcription. Nucleic Acids Res. 2001;29:4114-24 pubmed
  4. Ciarmatori S, Scott P, Sutcliffe J, McLees A, Alzuherri H, Dannenberg J, et al. Overlapping functions of the pRb family in the regulation of rRNA synthesis. Mol Cell Biol. 2001;21:5806-14 pubmed
    ..This reflects an ability of p130 to bind and inactivate the upstream binding factor, UBF. The data imply that rRNA synthesis in living cells is subject to redundant control by endogenous pRb and p130. ..
  5. Panova T, Panov K, Russell J, Zomerdijk J. Casein kinase 2 associates with initiation-competent RNA polymerase I and has multiple roles in ribosomal DNA transcription. Mol Cell Biol. 2006;26:5957-68 pubmed
    ..Thus, CK2 has the potential to regulate Pol I transcription at multiple levels, in PIC formation, activation, and reinitiation of transcription. ..
  6. Moorefield B, Greene E, Reeder R. RNA polymerase I transcription factor Rrn3 is functionally conserved between yeast and human. Proc Natl Acad Sci U S A. 2000;97:4724-9 pubmed
    ..Rrn3 is the first RNA polymerase I-specific transcription factor shown to be functionally conserved between yeast and mammals, suggesting that at least one mechanism that regulates ribosomal RNA synthesis is conserved among eukaryotes. ..
  7. Bierhoff H, Dundr M, Michels A, Grummt I. Phosphorylation by casein kinase 2 facilitates rRNA gene transcription by promoting dissociation of TIF-IA from elongating RNA polymerase I. Mol Cell Biol. 2008;28:4988-98 pubmed publisher
    ..The results reveal a mechanism by which the functional interplay between CK2 and FCP1 sustains multiple rounds of Pol I transcription. ..
  8. Valdez B, Henning D, So R, Dixon J, Dixon M. The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor. Proc Natl Acad Sci U S A. 2004;101:10709-14 pubmed
    ..The elucidation of a physiological function of treacle provides important information of relevance to the molecular dissection of the biochemical pathology of TCS. ..
  9. Kopp K, Gasiorowski J, Chen D, Gilmore R, Norton J, Wang C, et al. Pol I transcription and pre-rRNA processing are coordinated in a transcription-dependent manner in mammalian cells. Mol Biol Cell. 2007;18:394-403 pubmed
    ..Our observations suggest a model for sequential recruitment of pol I transcription factors and pre-rRNA processing factors to elongating pre-rRNA on an as-needed basis rather than corecruitment to sites of active transcription. ..
  10. Baserga R. Is cell size important?. Cell Cycle. 2007;6:814-6 pubmed
    ..This is probably due to the fact that the IGF-IR is more effective than the InR in translocationg to the nuclei IRS-1, which then binds UBF1, one of the proteins that regulate RNA pol I activity. ..
  11. Bodem J, Dobreva G, Hoffmann Rohrer U, Iben S, Zentgraf H, Delius H, et al. TIF-IA, the factor mediating growth-dependent control of ribosomal RNA synthesis, is the mammalian homolog of yeast Rrn3p. EMBO Rep. 2000;1:171-5 pubmed
    ..We demonstrate that TIF-IA interacts with Pol I in the absence of template DNA, augments Pol I transcription in vivo and rescues transcription in extracts from growth-arrested cells in vitro. ..
  12. Heix J, Zomerdijk J, Ravanpay A, Tjian R, Grummt I. Cloning of murine RNA polymerase I-specific TAF factors: conserved interactions between the subunits of the species-specific transcription initiation factor TIF-IB/SL1. Proc Natl Acad Sci U S A. 1997;94:1733-8 pubmed
    ..rodent promoter selectivity mediated by the TBP-TAFI complex is likely to be the result of cumulative subtle differences between individual subunits that lead to species-specific properties of RNA polymerase I transcription. ..
  13. McStay B, Frazier M, Reeder R. xUBF contains a novel dimerization domain essential for RNA polymerase I transcription. Genes Dev. 1991;5:1957-68 pubmed
    ..This suggests that the gap region has a critical function in transcription distinct from any effect on dimerization or DNA binding. ..
  14. Dundr M, Hoffmann Rohrer U, Hu Q, Grummt I, Rothblum L, Phair R, et al. A kinetic framework for a mammalian RNA polymerase in vivo. Science. 2002;298:1623-6 pubmed
    ..Our data provide a kinetic and mechanistic framework for the function of a mammalian RNA polymerase in living cells. ..
  15. Young D, Hassan M, Pratap J, Galindo M, Zaidi S, Lee S, et al. Mitotic occupancy and lineage-specific transcriptional control of rRNA genes by Runx2. Nature. 2007;445:442-6 pubmed
    ..Our results suggest that lineage-specific control of ribosomal biogenesis may be a fundamental function of transcription factors that govern cell fate. ..
  16. McStay B, Hu C, Pikaard C, Reeder R. xUBF and Rib 1 are both required for formation of a stable polymerase I promoter complex in X. laevis. EMBO J. 1991;10:2297-303 pubmed
    ..xUBF is closely similar in amino acid sequence to its previously reported human homolog, hUBF, except that xUBF has only three of the HMG-related domains while hUBF has four and therefore is 63 amino acids longer than xUBF. ..
  17. Cavanaugh A, Hirschler Laszkiewicz I, Hu Q, Dundr M, Smink T, Misteli T, et al. Rrn3 phosphorylation is a regulatory checkpoint for ribosome biogenesis. J Biol Chem. 2002;277:27423-32 pubmed
    ..These results suggest that the phosphorylation state of Rrn3 regulates rDNA transcription by determining the steady-state concentration of the Rrn3.RNA polymerase I complex within the nucleolus. ..
  18. O Sullivan A, Sullivan G, McStay B. UBF binding in vivo is not restricted to regulatory sequences within the vertebrate ribosomal DNA repeat. Mol Cell Biol. 2002;22:657-68 pubmed
    ..These results are consistent with a structural role for UBF at active nucleolar organizer regions in addition to its recognized role in stable transcription complex formation at the promoter...
  19. Cavanaugh A, Hempel W, Taylor L, Rogalsky V, Todorov G, Rothblum L. Activity of RNA polymerase I transcription factor UBF blocked by Rb gene product. Nature. 1995;374:177-80 pubmed
    ..These results indicate that there is an additional mechanism by which Rb suppresses cell growth, namely that Rb directly represses transcription of the rRNA genes. ..
  20. Sanij E, Poortinga G, Sharkey K, Hung S, Holloway T, Quin J, et al. UBF levels determine the number of active ribosomal RNA genes in mammals. J Cell Biol. 2008;183:1259-74 pubmed publisher
    ..We also show that the active rRNA gene pool is not static but decreases during differentiation, correlating with diminished UBF expression. Thus, UBF1 levels regulate active rRNA gene chromatin during growth and differentiation. ..
  21. Roussel P, Andre C, Masson C, Geraud G, Hernandez Verdun D. Localization of the RNA polymerase I transcription factor hUBF during the cell cycle. J Cell Sci. 1993;104 ( Pt 2):327-37 pubmed
    ..The relationship between proteins associated with the NORs and ribosomal gene transcription is discussed...
  22. Voit R, Grummt I. Phosphorylation of UBF at serine 388 is required for interaction with RNA polymerase I and activation of rDNA transcription. Proc Natl Acad Sci U S A. 2001;98:13631-6 pubmed
    ..The results suggest that phosphorylation of UBF represents a powerful means of modulating the assembly of the transcription initiation complex in a proliferation- and cell cycle-dependent fashion. ..
  23. Beckouët F, Labarre Mariotte S, Albert B, Imazawa Y, Werner M, Gadal O, et al. Two RNA polymerase I subunits control the binding and release of Rrn3 during transcription. Mol Cell Biol. 2008;28:1596-605 pubmed
    ..These data suggest a dual role of the Rpa49-Rpa34 dimer during the recruitment of Rrn3 and its subsequent dissociation from the elongating polymerase. ..
  24. Mais C, Wright J, Prieto J, Raggett S, McStay B. UBF-binding site arrays form pseudo-NORs and sequester the RNA polymerase I transcription machinery. Genes Dev. 2005;19:50-64 pubmed
    ..Furthermore, we propose that UBF mediates recruitment of the pol I machinery to nucleoli independently of promoter elements...
  25. Prieto J, McStay B. Recruitment of factors linking transcription and processing of pre-rRNA to NOR chromatin is UBF-dependent and occurs independent of transcription in human cells. Genes Dev. 2007;21:2041-54 pubmed
    ..Taken together, these results highlight the importance of the specialized chromatin structure at active NORs in coordinating early events in ribosome biogenesis and nucleolar formation...
  26. Grummt I. Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev. 2003;17:1691-702 pubmed
  27. Lee J, Hwang Y, Boo J, Han D, Kwon O, Todorova K, et al. Dysregulation of upstream binding factor-1 acetylation at K352 is linked to impaired ribosomal DNA transcription in Huntington's disease. Cell Death Differ. 2011;18:1726-35 pubmed publisher
    ..This novel mechanism suggests that modulation of UBF-mediated rDNA synthesis by CBP may be a therapeutic target for improving neuronal rDNA transcription in HD. ..
  28. Hannan K, Hannan R, Smith S, Jefferson L, Lun M, Rothblum L. Rb and p130 regulate RNA polymerase I transcription: Rb disrupts the interaction between UBF and SL-1. Oncogene. 2000;19:4988-99 pubmed
    ..These results suggest that p130 may regulate rDNA transcription in a similar manner to Rb. ..
  29. Zhao J, Yuan X, Frodin M, Grummt I. ERK-dependent phosphorylation of the transcription initiation factor TIF-IA is required for RNA polymerase I transcription and cell growth. Mol Cell. 2003;11:405-13 pubmed
    ..The results provide a link between growth factor signaling, ribosome production, and cell growth, and may have a major impact on the mechanism of cell transformation. ..
  30. Philippi A, Steinbauer R, Reiter A, Fath S, Leger Silvestre I, Milkereit P, et al. TOR-dependent reduction in the expression level of Rrn3p lowers the activity of the yeast RNA Pol I machinery, but does not account for the strong inhibition of rRNA production. Nucleic Acids Res. 2010;38:5315-26 pubmed publisher
    ..However, our analysis reveals that the dramatic reduction of rRNA synthesis in the immediate cellular response to impaired TOR signalling cannot be explained by the simple down-regulation of Rrn3p and Pol I-Rrn3p levels. ..
  31. Friedrich J, Panov K, Cabart P, Russell J, Zomerdijk J. TBP-TAF complex SL1 directs RNA polymerase I pre-initiation complex formation and stabilizes upstream binding factor at the rDNA promoter. J Biol Chem. 2005;280:29551-8 pubmed
  32. Lin C, Tuan J, Scalia P, Bui T, Comai L. The cell cycle regulatory factor TAF1 stimulates ribosomal DNA transcription by binding to the activator UBF. Curr Biol. 2002;12:2142-6 pubmed
    ..Thus, TAF1 may be involved in the coordinate expression of Pol I- and Pol II-transcribed genes required for protein biosynthesis and cell cycle progression. ..
  33. Stefanovsky V, Pelletier G, Bazett Jones D, Crane Robinson C, Moss T. DNA looping in the RNA polymerase I enhancesome is the result of non-cooperative in-phase bending by two UBF molecules. Nucleic Acids Res. 2001;29:3241-7 pubmed
    ..We use this and previous data to refine the existing enhancesome model and show that HMG boxes 1 and 2 of UBF lie head-to-head along the DNA. ..
  34. Hannan K, Brandenburger Y, Jenkins A, Sharkey K, Cavanaugh A, Rothblum L, et al. mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF. Mol Cell Biol. 2003;23:8862-77 pubmed
    ..Thus, mTOR plays a critical role in the regulation of ribosome biogenesis via a mechanism that requires S6K1 activation and phosphorylation of UBF. ..
  35. Hanada K, Song C, Yamamoto K, Yano K, Maeda Y, Yamaguchi K, et al. RNA polymerase I associated factor 53 binds to the nucleolar transcription factor UBF and functions in specific rDNA transcription. EMBO J. 1996;15:2217-26 pubmed
  36. Fath S, Milkereit P, Peyroche G, Riva M, Carles C, Tschochner H. Differential roles of phosphorylation in the formation of transcriptional active RNA polymerase I. Proc Natl Acad Sci U S A. 2001;98:14334-9 pubmed
    ..We suggest that phosphorylation at specific sites of pol I is a prerequisite for proper transcription initiation and that phosphorylation/dephosphorylation of pol I is one possibility to modulate cellular rDNA transcription activity. ..
  37. Sirri V, Roussel P, Hernandez Verdun D. The mitotically phosphorylated form of the transcription termination factor TTF-1 is associated with the repressed rDNA transcription machinery. J Cell Sci. 1999;112 ( Pt 19):3259-68 pubmed
    ..The reorganization of the mitotic rDNA promoter might be induced by phosphorylation of certain components of the rDNA transcription machinery and participate in silencing of rDNA during mitosis...
  38. Chan E, Imai H, Hamel J, Tan E. 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. J Exp Med. 1991;174:1239-44 pubmed
    ..Furthermore, we identified a nucleolar transcription factor as a novel target for human autoimmune response...
  39. Hempel W, Cavanaugh A, Hannan R, Taylor L, Rothblum L. The species-specific RNA polymerase I transcription factor SL-1 binds to upstream binding factor. Mol Cell Biol. 1996;16:557-63 pubmed
    ..These data provide evidence that UBF and SL-1 interact. ..
  40. Bol var J, Goenechea L, Grenett H, Pend n C, Valdivia M. Cloning and sequencing of the genes encoding the hamster ribosomal transcription factors UBF1 and UBF2. Gene. 1996;176:257-8 pubmed
    ..This insertion is completely conserved among mammalian UBF1 which indicates a putative role of this region on the function of this transcript...
  41. Milkereit P, Tschochner H. A specialized form of RNA polymerase I, essential for initiation and growth-dependent regulation of rRNA synthesis, is disrupted during transcription. EMBO J. 1998;17:3692-703 pubmed
    ..We propose that the formation and disruption of the pol I-Rrn3p complex reflects a molecular switch for regulating rRNA synthesis and its growth rate-dependent regulation. ..
  42. Miller G, Panov K, Friedrich J, Trinkle Mulcahy L, Lamond A, Zomerdijk J. hRRN3 is essential in the SL1-mediated recruitment of RNA Polymerase I to rRNA gene promoters. EMBO J. 2001;20:1373-82 pubmed
    ..We conclude that hRRN3 functions to recruit initiation-competent Pol I to rRNA gene promoters. The essential role for hRRN3 in linking Pol I to SL1 suggests a mechanism for growth control of Pol I transcription. ..
  43. Panov K, Panova T, Gadal O, Nishiyama K, Saito T, Russell J, et al. RNA polymerase I-specific subunit CAST/hPAF49 has a role in the activation of transcription by upstream binding factor. Mol Cell Biol. 2006;26:5436-48 pubmed
  44. Pelletier G, Stefanovsky V, Faubladier M, Hirschler Laszkiewicz I, Savard J, Rothblum L, et al. Competitive recruitment of CBP and Rb-HDAC regulates UBF acetylation and ribosomal transcription. Mol Cell. 2000;6:1059-66 pubmed
    ..quot; Thus, PolI transcription is regulated by protein acetylation, and the competitive recruitment of CBP and Rb. ..
  45. Panov K, Friedrich J, Russell J, Zomerdijk J. UBF activates RNA polymerase I transcription by stimulating promoter escape. EMBO J. 2006;25:3310-22 pubmed
    ..We posit that stimulation of promoter escape could be a general mechanism of activator function. ..
  46. Casafont I, Bengoechea R, Navascues J, Pena E, Berciano M, Lafarga M. The giant fibrillar center: a nucleolar structure enriched in upstream binding factor (UBF) that appears in transcriptionally more active sensory ganglia neurons. J Struct Biol. 2007;159:451-61 pubmed
    ..We suggest that the formation of GFCs is associated with a high rate of ribosome biogenesis of the transcriptionally more active large-size neurons. ..
  47. Gébrane Younès J, Fomproix N, Hernandez Verdun D. When rDNA transcription is arrested during mitosis, UBF is still associated with non-condensed rDNA. J Cell Sci. 1997;110 ( Pt 19):2429-40 pubmed
    ..It is proposed that modifications of the transcription machinery occurring in prometaphase could explain the arrest of transcription, while reverse modifications in late anaphase could explain activation...
  48. Claypool J, French S, Johzuka K, Eliason K, Vu L, Dodd J, et al. Tor pathway regulates Rrn3p-dependent recruitment of yeast RNA polymerase I to the promoter but does not participate in alteration of the number of active genes. Mol Biol Cell. 2004;15:946-56 pubmed
  49. Keys D, Vu L, Steffan J, Dodd J, Yamamoto R, Nogi Y, et al. RRN6 and RRN7 encode subunits of a multiprotein complex essential for the initiation of rDNA transcription by RNA polymerase I in Saccharomyces cerevisiae. Genes Dev. 1994;8:2349-62 pubmed
    ..These observations are discussed in comparison to in vitro rDNA transcription systems from higher eukaryotes. ..
  50. O Mahony D, Rothblum L. Identification of two forms of the RNA polymerase I transcription factor UBF. Proc Natl Acad Sci U S A. 1991;88:3180-4 pubmed
    ..Thus, the existence of different forms of UBF may have important ramifications for transcription by RNA polymerase I. ..
  51. Poortinga G, Hannan K, Snelling H, Walkley C, Jenkins A, Sharkey K, et al. MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation. EMBO J. 2004;23:3325-35 pubmed
  52. Stefanovsky V, Pelletier G, Hannan R, Gagnon Kugler T, Rothblum L, Moss T. An immediate response of ribosomal transcription to growth factor stimulation in mammals is mediated by ERK phosphorylation of UBF. Mol Cell. 2001;8:1063-73 pubmed
    ..Thus, growth factor regulation of ribosomal transcription likely acts by a cyclic modulation of DNA architecture. The data suggest a central role for ribosome biogenesis in growth regulation. ..
  53. Grueneberg D, Pablo L, Hu K, August P, Weng Z, Papkoff J. A functional screen in human cells identifies UBF2 as an RNA polymerase II transcription factor that enhances the beta-catenin signaling pathway. Mol Cell Biol. 2003;23:3936-50 pubmed