Skip to main content

The RNA Polymerase I Transcription Machinery

  • Chapter
  • First Online:
The Nucleolus

Part of the book series: Protein Reviews ((PRON,volume 15))

  • 1589 Accesses

Abstract

In this chapter, we review transcription of mammalian rRNA genes by RNA polymerase I (Pol I), a process that integrates information from cellular signaling cascades to regulate ribosome production. Although the emerging picture of Pol I transcriptional regulation reveals an unexpected level of complexity, we are beginning to understand the multiple links between the Pol I transcription machinery and the sophisticated network of signaling cascades that guide cell growth and proliferation. A comprehensive analysis of the connection between Pol I transcription, cell proliferation, and growth-factor signaling has not only expanded our understanding of the molecular mechanisms that control rRNA synthesis and ribosome biogenesis but will also facilitate the development of new strategies that inhibit ribosome biogenesis, and hence proliferation of cancer cells, through targeted downregulation of components of the Pol I transcription apparatus.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Alzuherri HM, White RJ (1999) Regulation of RNA polymerase I transcription in response to F9 embryonal carcinoma stem cell differentiation. J Biol Chem 274:4328–4334

    PubMed  CAS  Google Scholar 

  • Arabi A, Wu S, Ridderstrale K, Bierhoff H, Shiue C et al (2005) c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription. Nat Cell Biol 7:303–310

    PubMed  CAS  Google Scholar 

  • Ashraf N, Zino S, Macintyre A, Kingsmore D, Payne AP, George WD, Shiels PG (2006) Altered sirtuin expression is associated with node-positive breast cancer. Br J Cancer 95:1056–1061

    PubMed  CAS  Google Scholar 

  • Beck T, Hall MN (1999) The TOR signaling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature 402:689–692

    PubMed  CAS  Google Scholar 

  • Bettinger BT, Gilbert DM, Amberg DC (2004) Actin up in the nucleus. Nat Rev Mol Cell Biol 5:410–415

    PubMed  CAS  Google Scholar 

  • Bierhoff H, Dundr M, Michels A, Grummt I (2008) Phosphorylation by CK2 facilitates rDNA transcription by promoting dissociation of TIF-IA from elongating RNA polymerase. Mol Cell Biol 28:4988–4998

    PubMed  CAS  Google Scholar 

  • Birch JL, Tan BC, Panov KI, Panova TB, Andersen JS, Owen-Hughes TA, Russell J, Lee SC, Zomerdijk JC (2009) FACT facilitates chromatin transcription by RNA polymerases I and III. EMBO J 28:854–865

    PubMed  CAS  Google Scholar 

  • Blander G, Guarente L (2004) The Sir2 family of protein deacetylases. Ann Rev Biochem 73:417–435

    PubMed  CAS  Google Scholar 

  • Bodem J, Dobreva G, Hoffmann-Rohrer U, Iben S, Zentgraf H, Delius H, Vingron M, Grummt I (2000) TIF-IA, the factor mediating growth-dependent control of ribosomal RNA synthesis, is the mammalian homolog of yeast Rrn3p. EMBO Rep 1:171–175

    PubMed  CAS  Google Scholar 

  • Boulon S, Westman BJ, Hutten S, Boisvert FM, Lamond AI (2010) The nucleolus under stress. Mol Cell 40:216–227

    PubMed  CAS  Google Scholar 

  • Cavanaugh AH, Hempel WM, Taylor LJ, Rogalsky V, Todorov G, Rothblum LI (1995) Activity of RNA polymerase I transcription factor UBF blocked by Rb gene product. Nature 374:177–180

    PubMed  CAS  Google Scholar 

  • Chen D, Dundr M, Wang C, Leung A, Lamond A, Misteli T, Huang S (2005) Condensed mitotic chromatin is accessible to transcription factors and chromatin structural proteins. J Cell Biol 168:41–54

    PubMed  CAS  Google Scholar 

  • Ciarmatori S, Scott PH, Sutcliffe JE, McLees A, Alzuherri HM, Dannenberg JH, te Riele H, Grummt I, Voit R, White RJ (2001) Overlapping functions of the pRb family in the regulation of rRNA synthesis. Mol Cell Biol 21:5806–5814

    PubMed  CAS  Google Scholar 

  • Claypool JA et al (2004) 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 15:946–956

    PubMed  CAS  Google Scholar 

  • Clos J, Buttgereit D, Grummt I (1986) A purified transcription factor (TIF-IB) binds to essential sequences of the mouse rDNA promoter. Proc Natl Acad Sci 83:604–608

    PubMed  CAS  Google Scholar 

  • Comai L, Tanese N, Tjian R (1992) The TATA-binding protein and associated factors are integral components of the RNA polymerase I transcription factor, SL1. Cell 68:965–976

    PubMed  CAS  Google Scholar 

  • Cremer P, Armache KJ, Baumli S, Benkert S, Brueckner F, Buchen C, Damsma GE, Dengl S, Geiger SR, Jasiak AJ, Jawhari A, Jennebach S, Kamenski T, Kettenberger H, Kuhn CD, Lehmann E, Leike K, Sydow JF, Vannini A (2008) Structure of eukaryotic RNA polymerases. Ann Rev Biophys 37:337–352

    Google Scholar 

  • Denissov S, van Driel M, Voit R, Hekkelman M, Hulsen T, Hernandez N, Grummt I, Wehrens R, Stunnenberg H (2007) Identification of novel functional TBP-binding sites and general factor repertoires. EMBO J 26:944–954

    PubMed  CAS  Google Scholar 

  • Dundr M, Hoffmann-Rohrer U, Hu Q, Grummt I, Rothblum LI, Phair RD, Misteli T (2002) A kinetic framework for a mammalian RNA polymerase in vivo. Science 298:1623–1626

    PubMed  CAS  Google Scholar 

  • Evers R, Grummt I (1995) Molecular coevolution of mammalian ribosomal gene terminator sequences and the transcription termination factor TTF-I. Proc Natl Acad Sci USA 92:5827–3581

    PubMed  CAS  Google Scholar 

  • Evers R, Smid A, Rudloff U, Lottspeich F, Grummt I (1995) Different domains of the murine RNA polymerase I-specific termination factor mTTF-I serve distinct functions in transcription termination. EMBO J 14:1248–1256

    PubMed  CAS  Google Scholar 

  • Fomproix N, Percipalle P (2004) An actin-myosin complex on actively transcribing genes. Exp Cell Res 294:140–148

    PubMed  CAS  Google Scholar 

  • Ford E, Voit R, Liszt G, Magin C, Grummt I, Guarente L (2006) Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes Dev 20:1075–1080

    PubMed  CAS  Google Scholar 

  • French SL, Osheim YN, Cioci F, Nomura M, Beyer AL (2003) In exponentially growing Saccharomyces cerevisiae cells, rRNA synthesis is determined by the summed RNA polymerase I loading rate rather than by the number of active genes. Mol Cell Biol 23:1558–1568

    PubMed  CAS  Google Scholar 

  • Geiger SR, Lorenzen K, Schreieck A, Hanecker P, Kostrewa D, Heck AJR, Cramer P (2010) RNA polymerase I contains a TFIIF-related DNA-binding subcomplex. Mol Cell 39:583–594

    PubMed  CAS  Google Scholar 

  • Gerber JK, Gögel E, Berger C, Wallisch M, Müller F, Grummt I, Grummt F (1997) Termination of mammalian rDNA replication: polar arrest of replication fork movement by transcription termination factor TTF-I. Cell 90:559–567

    PubMed  CAS  Google Scholar 

  • Gomez-Roman N, Felton-Edkins ZA, Kenneth NS, Goodfellow SJ, Athineos D, Zhang J, Ramsbottom BA, Innes F, Kantidakis T, Kerr ER, Brodie G, Grandori C, White RJ (2006) Activation by c-myc of transcription by RNA polymerases I, II and III. Biochem Soc Symp 73:141–154

    PubMed  CAS  Google Scholar 

  • Gorski JJ, Pathak S, Panov K, Kasciukovic T, Panova T, Russell J, Zomerdijk JCBM (2007) A novel TBP-associated factor of SL1 functions in RNA polymerase I transcription. EMBO J 26:1560–1568

    PubMed  CAS  Google Scholar 

  • Gorski SA, Snyder SK, John S, Grummt I, Misteli T (2008) Modulation of RNA polymerase assembly dynamics in transcription regulation. Mol Cell 30:486–497

    PubMed  CAS  Google Scholar 

  • Grandori C, Gomez-Roman N, Felton-Edkins ZA, Ngouenet C, Galloway DA et al (2005) c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nat Cell Biol 7:311–318

    PubMed  CAS  Google Scholar 

  • Grob A, Roussel P, Wright JE, McStay B, Hernandez-Verdun D, Sirri V (2009) Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis. J Cell Sci 122:489–498

    PubMed  CAS  Google Scholar 

  • Grummt I (2006) Actin and myosin as transcription factors. Curr Opin Biol Genet Dev 16:191–196

    CAS  Google Scholar 

  • Grummt I (2010) Wisely chosen paths - regulation of rRNA synthesis. FEBS J 277:4626–2639

    PubMed  CAS  Google Scholar 

  • Grummt I, Grummt F (1976) Control of nucleolar RNA synthesis by the intracellular pool sizes of ATP and GTP. Cell 7:447–453

    PubMed  CAS  Google Scholar 

  • Grummt I, Voit R (2010) Linking rDNA transcription to the cellular energy supply. Cell Cycle 9:18–19

    Google Scholar 

  • Grummt I, Smith VA, Grummt F (1976) Amino acid starvation affects the initiation frequency of nucleolar RNA polymerase. Cell 7:439–445

    PubMed  CAS  Google Scholar 

  • Grummt I, Maier U, Öhrlein A, Hassouna N, Bachellerie JP (1985) Transcription of mouse rDNA terminates downstream of the 3’ end of 28 S RNA and involves interaction of factors with repeated sequences in the 3’ spacer. Cell 43:801–810

    PubMed  CAS  Google Scholar 

  • Grummt I, Kuhn A, Bartsch I, Rosenbauer H (1986a) A transcription terminator located upstream of the mouse rDNA initiation site affects rRNA synthesis. Cell 47:901–911

    PubMed  CAS  Google Scholar 

  • Grummt I, Rosenbauer H, Niedermeyer I, Maier U, Öhrlein A (1986b) A repeated 18 bp sequence motif in the mouse rDNA spacer mediates binding of a nuclear factor and transcription termination. Cell 45:837–846

    PubMed  CAS  Google Scholar 

  • Hanada K, Song CZ, Yamamoto K, Yano K, Maeda Y, Yamaguchi K, Muramatsu M (1996) RNA polymerase I associated factor 53 binds to the nucleolar transcription factor UBF and functions in specific rDNA transcription. EMBO J 15:2217–2226

    PubMed  CAS  Google Scholar 

  • Hannan KM, Brandenburger Y, Jenkins A, Sharkey K, Cavanaugh A et al (2003) 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 23:8862–8877

    PubMed  CAS  Google Scholar 

  • Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8:774–785

    PubMed  CAS  Google Scholar 

  • Heix J, Zomerdijk JCBM, Ravanpay A, Tjian R, Grummt I (1997) Cloning of murine RNA polymerase I- specific TAFs: Conserved interactions between the four sub- units of the species-specific transcription factor TIF-IB/SL1. Proc Natl Acad Sci 94:1733–1738

    PubMed  CAS  Google Scholar 

  • Heix J, Vente A, Voit R, Budde A, Michaelidis TM, Grummt I (1998) Mitotic silencing of human rRNA synthe- sis: Inactivation of the promoter selectivity factor SL1 by cdc2/cyclin B-mediated phosphorylation. EMBO J 17:7373–7381

    PubMed  CAS  Google Scholar 

  • Henderson S, Sollner-Webb B (1986) A transcriptional terminator is a novel element of the promoter of the mouse ribosomal RNA gene. Cell 47:891–900

    PubMed  CAS  Google Scholar 

  • Hirschler-Laszkiewicz I, Cavanaugh A, Hu Q, Catania J, Avantaggiati ML, Rothblum LI (2001) The role of acetylation in rDNA transcription. Nucleic Acids Res 29:4114–4124

    PubMed  CAS  Google Scholar 

  • Hoppe S, Bierhoff H, Cado I, Weber A, Tiebe M, Grummt I, Voit R (2009) AMP-activated protein kinase adapts rRNA synthesis to cellular energy supply. Proc Natl Acad Sci USA 106:17781–17786

    PubMed  CAS  Google Scholar 

  • Itahana K, Bhat KP, Jin A, Itahana Y, Hawke D, Kobayasi R, Zhang Y (2003) Tunor suppressor ARF degrades B23, a nucleolar protein involved in ribosome biogenesis and cell proliferation. Mol Cell 12:1151–1161

    PubMed  CAS  Google Scholar 

  • James MJ, Zomerdijk JC (2004) Phosphatidylinositol 3-kinase and mTOR signaling pathways regulate RNA polymerase I transcription in response to IGF-1 and nutrients. J Biol Chem 279:8911–8918

    PubMed  CAS  Google Scholar 

  • Jansa P, Mason SW, Hoffmann-Rohrer U, Grummt I (1998) Cloning and functional characterization of PTRF, a novel protein which induces dissociation of paused ternary transcription complexes. EMBO J 17:2855–2864

    PubMed  CAS  Google Scholar 

  • Jantzen HM, Admon A, Bell SP, Tjian R (1990) Nucleolar transcription factor hUBF contains a DNA-binding motif with homology to HMG protein. Nature 344:830–836

    PubMed  CAS  Google Scholar 

  • Klein J, Grummt I (1999) Cell cycle-dependent regulation of RNA polymerase I transcription: The nucleolar transcription factor UBF is inactive in mitosis and early G1. Proc Natl Acad Sci 96:6095–6101

    Google Scholar 

  • Kuhn A, Grummt I (1992) Dual role of the nucleolar transcription factor UBF: trans-activator and antirepressor. Proc Natl Acad Sci 89:7340–7344

    PubMed  CAS  Google Scholar 

  • Kuhn A, Stefanovsky V, Grummt I (1993) The nucleolar transcription activator UBF relieves Ku antigen-mediated repression of mouse ribosomal gene transcription. Nucleic Acids Res 21:2057–2063

    PubMed  CAS  Google Scholar 

  • Kuhn A, Vente A, Dorée M, Grummt I (1998) Mitotic phosphorylation of the TBP-containing factor SL1 represses ribosomal gene transcription. J Mol Biol 284:1–5

    PubMed  CAS  Google Scholar 

  • Kuhn CD, Geiger SR, Baumli S, Gartmann M, Gerber J, Jennebach S, Mielke T, Tschochner H, Beckmann R, Cramer P (2007) Functional architecture of RNA polymerase I. Cell 131:1260–1272

    PubMed  CAS  Google Scholar 

  • Kulkens T, van der Sande CA, Dekker AF, van Heerikhuizen H, Planta RJ (1992) A system to study transcription by yeast RNA polymerase I within the chromosomal context: functional analysis of the ribosomal DNA enhancer and the RBP1/REB1 binding sites. EMBO J 11:4665–4674

    PubMed  CAS  Google Scholar 

  • Kysela K, Philimonenko AA, Philimonenko VV, Janacek J, Kahle M, Hozak P (2005) Nuclear distribution of actin and myosin I depends on transcriptional activity of the cell. Histochem Cell Biol 124:347–358

    PubMed  CAS  Google Scholar 

  • Längst G, Blank TA, Becker PB, Grummt I (1997) RNA polymerase I transcription on nucleosomal templates: the transcription termination factor TTF-I induces chromatin remodeling and relieves transcriptional repression. EMBO J 16:760–768

    PubMed  Google Scholar 

  • Längst G, Becker PB, Grummt I (1998) TTF-I determines the chromatin architecture of the active rDNA promoter. EMBO J 17:3135–3145

    PubMed  Google Scholar 

  • Learned RM, Cordes S, Tjian R (1985) Purification and characterization of a transcription factor that confers promoter specificity to human RNA poymerase I. Mol Cell Biol 5:1358–1369

    PubMed  CAS  Google Scholar 

  • Lessard F, Morin F, Ivanchuk S, Langlois F, Stefanovsky V, Rutka J, Moss T (2010) The ARF tumor suppressor controls ribosome biogenesis by regulating the RNA polymerase I transcription factor TTF-I. Mol Cell 38:539–550

    PubMed  CAS  Google Scholar 

  • Leung AK, Gerlich D, Miller G, Lyon C, Lam YW, Lleres D, Daigle N, Zomerdijk J, Ellenberg J, Lamond AI (2004) Quantitative linetic analysis of nucleolar breakdown and reassembly during mitosis in live human cells. J Cell Biol 166:787–800

    PubMed  CAS  Google Scholar 

  • Lin CY, Navarro S, Reddy S, Comai L (2006) CK2-mediated stimulation of Pol I transcription by stabilization of UBF-SL1 interaction. Nucleic Acids Res 34:4752–4766

    PubMed  CAS  Google Scholar 

  • Marilley M, Pasero P (1996) Common DNA structural features exhibited by eukaryotic ribosomal gene promoters. Nucleic Acids Res 24:2204–2211

    PubMed  CAS  Google Scholar 

  • Mayer C, Zhao J, Yuan X, Grummt I (2004) mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability. Genes Dev 18:423–434

    PubMed  CAS  Google Scholar 

  • Mayer C, Bierhoff H, Grummt I (2005) The nucleolus as a stress sensor: JNK2 inactivates the transcription factor TIF-IA and down-regulates rRNA synthesis. Genes Dev 19:933–941

    Google Scholar 

  • McStay B, Reeder RH (1990) An RNA polymerase I termination site can stimulate the adjacent ribosomal gene promoter by two distinct mechanisms in Xenopus laevis. Genes Dev 4:1240–1251

    PubMed  CAS  Google Scholar 

  • Meraner J, Lechner M, Loidl A, Goralik-Schramel M, Voit R, Grummt I, Loidl P (2006) Acetylation of UBF changes during the cell cycle and regulates the interaction of UBF with RNA polymerase I. Nucleic Acids Res 34:1798–1806

    PubMed  CAS  Google Scholar 

  • Miller G, Panov KI, Friedrich JK, Trinkle-Mulcahy L, Lamond AI, Zomerdijk JC (2001) hRRN3 is essential in the SL1-mediated recruitment of RNA Polymerase I to rRNA gene promoters. EMBO J 20:1373–1382

    PubMed  CAS  Google Scholar 

  • Moorefield B, Greene EA, Reeder RH (2000) RNA polymerase I transcription factor Rrn3 is functionally conserved between yeast and human. Proc Natl Acad Sci USA 97:4724–4729

    PubMed  CAS  Google Scholar 

  • Moss T (2004) At the crossroads of growth control; making ribosomal RNA. Curr Opin Genet Dev 14:210–217

    PubMed  CAS  Google Scholar 

  • Moss T, Langlois F, Gagnon-Kugler T, Stefanovsky V (2007) A housekeeper with power of attorney: the rRNA genes in ribosome biogenesis. Cell Mol Life Sci 64:29–49

    PubMed  CAS  Google Scholar 

  • Murano K, Okuwaki M, Hisaoka M, Nagata K (2008) Transcription regulation of the rRNA gene by a multifunctional nucleolar protein, B23/nucleophosmin, through its histone chaperone activity. Mol Cell Biol 28:3114–3126

    PubMed  CAS  Google Scholar 

  • Muth V, Nadaud S, Grummt I, Voit R (2001) Acetylation of TAFI68, a subunit of TIF-IB/SL1, activates RNA polymerase I transcription. EMBO J 20:1353–1362

    PubMed  CAS  Google Scholar 

  • Németh A, Guibert S, Tiwari VK, Ohlsson R, Längst G (2008) Epigenetic regulation of TTF-I-mediated promoter-terminator interactions of rRNA genes. EMBO J 27:1255–1265

    PubMed  Google Scholar 

  • Nowak G, Pestic-Dragovich L, Hozák P, Philimonenko A, Simerly C, Schatten G, de Lanerolle P (1997) Evidence for the presence of myosin I in the nucleus. J Biol Chem 272:17176–17181

    PubMed  CAS  Google Scholar 

  • Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3:ra3

    Google Scholar 

  • Panov KI, Friedrich JK, Russell J, Zomerdijk JC (2006a) UBF activates RNA polymerase I transcription by stimulating promoter escape. EMBO J 25:3310–3322

    PubMed  CAS  Google Scholar 

  • Panov KI, Panova TB, Gadal O, Nishiyama K, Saito T, Russell J, Zomerdijk JC (2006b) RNA polymerase I-specific subunit CAST/hPAF49 has a role in the activation of transcription by upstream binding factor. Mol Cell Biol 26:5436–5448

    PubMed  CAS  Google Scholar 

  • Panova TB, Panov KI, Russell J, Zomerdijk JC (2006) Casein kinase 2 associates with initiation-competent RNA polymerase I and has multiple roles in ribosomal DNA transcription. Mol Cell Biol 26:5957–5968

    PubMed  CAS  Google Scholar 

  • Parlato R, Kreiner G, Erdmann G, Rieker C, Stotz S et al (2008) Activation of an endogenous suicide response after perturbation of rRNA synthesis leads to neurodegeneration in mice. J Neurosci 28:12759–12764

    PubMed  CAS  Google Scholar 

  • Pelletier G, Stefanovsky VY, Faubladier M, Hirschler-Laszkiewicz I, Savard J, Rothblum LI, Côté J, Moss T (2000) Competitive recruitment of CBP and Rb-HDAC regulates UBF acetylation and ribosomal transcription. Mol Cell 6:1059–1066

    PubMed  CAS  Google Scholar 

  • Percipalle P, Fomproix N, Cavellan E, Voit R, Reimer G, Kruger T, Thyberg J, Scheer U, Grummt I, Farrants AK (2006) The chromatin remodelling complex WSTF–SNF2h interacts with nuclear myosin 1 and has a role in RNA polymerase I transcription. EMBO Rep 7:525–530

    PubMed  CAS  Google Scholar 

  • Pestic-Dragovich L, Stojiljkovic L, Philimonenko AA, Nowak G, Ke Y, Settlage RE, Shabanowitz J, Hunt DF, Hozák P, de Lanerolle P (2000) A myosin I isoform in the nucleus. Science 290:337–341

    PubMed  CAS  Google Scholar 

  • Philimonenko VV, Zhao J, Iben S, Dingova H, Kysela K, Kahle M, Zentgraf H, Hofmann WA, de Lanerolle P, Hozak P, Grummt I (2004) Nuclear actin and myosin I are required for RNA polymerase I transcription. Nat Cell Biol 6:1165–1172

    PubMed  CAS  Google Scholar 

  • Philimonenko VV, Janacek J, Harata M, Hozak P (2010) Transcription-dependent rearrangements of actin and nuclear myosin I in the nucleolus. Histochem Cell Biol 133:607–626

    Google Scholar 

  • Poortinga G, Hannan KM, Snelling H, Walkley CR, Jenkins A, Sharkey K, Wall M, Brandenburger Y, Palatsides M, Pearson RB, McArthur GA, Hannan RD (2004) MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation. EMBO J 23:3325–3335

    PubMed  CAS  Google Scholar 

  • Rickards B, Flint SJ, Cole MD, Leroy G (2007) Nucleolin is required for RNA polymerase I transcription in vivo. Mol Cell Biol 27:937–948

    PubMed  CAS  Google Scholar 

  • Rieker C, Engblom D, Kreiner G, Schober A, Stotz S, Neumann M, Yuan X, Grummt I, Schütz G, Parlato R (2011) Nucleolar disruption in dopaminergic neurons leads to oxidative damage and Parkinsonism through repression of mTOR signaling. J Neurosci 31:453–460

    PubMed  CAS  Google Scholar 

  • Russell J, Zomerdijk JC (2005) RNA-polymerase-I-directed rDNA transcription, life and works. Trends Biochem Sci 30:87–96

    PubMed  CAS  Google Scholar 

  • Sander EE, Grummt I (1997) Oligomerization of the transcription termination factor TTF-I: implications for the structural organization of ribosomal transcription units. Nucleic Acids Res 25:1142–1147

    PubMed  CAS  Google Scholar 

  • Sander EE, Mason SW, Munz C, Grummt I (1996) The amino-terminal domain of the transcription termination factor TTF-I causes protein oligomerization and inhibition of DNA binding. Nucleic Acids Res 24:3677–3684

    PubMed  CAS  Google Scholar 

  • Sanij E, Poortinga G, Sharkey K, Hung S, Holloway TP, Quin J, Robb E, Wong LH, Thomas WG, Stefanovsky V, Moss T, Rothblum L, Hannan KM, McArthur GA, Pearson RB, Hannan RD (2008) UBF levels determine the number of active ribosomal RNA genes in mammals. J Cell Biol 183:1259–1274

    Google Scholar 

  • Smid A, Finsterer M, Grummt I (1992) Limited proteolysis unmasks specific DNA-binding of the murine RNA polymerase I-specific transcription termination factor TTFI. J Mol Biol 227:635–647

    PubMed  CAS  Google Scholar 

  • Stefanovsky VY, Pelletier G, Hannan R, Gagnon-Kugler T, Rothblum LI, Moss T (2001) An immediate response of ribosomal transcription to growth factor stimulation in mammals is mediated by ERK phosphorylation of UBF. Mol Cell 8:1063–1073

    PubMed  CAS  Google Scholar 

  • Stefanovsky V, Langlois F, Gagnon-Kugler T, Rothblum LI, Moss T (2006a) Growth factor signaling regulates elongation of RNA polymerase I transcription in mammals via UBF phosphorylation and r-chromatin remodeling. Mol Cell 21:629–639

    PubMed  CAS  Google Scholar 

  • Stefanovsky VY, Langlois F, Bazett-Jones D, Pelletier G, Moss T (2006b) ERK modulates DNA bending and enhancesome structure by phosphorylating HMG1-boxes 1 and 2 of the RNA polymerase I transcription factor UBF. Biochemistry 45:3626–3634

    PubMed  CAS  Google Scholar 

  • Voit R, Grummt I (2001) Phosphorylation of UBF at serine 388 is required for interaction with RNA polymerase I and activation of rDNA transcription. Proc Natl Acad Sci USA 98:13631–13636

    PubMed  CAS  Google Scholar 

  • Voit R, Schäfer K, Grummt I (1997) Mechanism of repression of RNA polymerase I transcription by the retinoblastoma protein. Mol Cell Biol 17:4230–4237

    PubMed  CAS  Google Scholar 

  • Voit R, Hoffmann M, Grummt I (1999) Phosphorylation by G1-specific cdk-cyclin complexes activates the nucleolar transcription factor UBF. EMBO J 18:1891–1899

    PubMed  CAS  Google Scholar 

  • Weisenberger D, Scheer U (1995) A possible mechanism for the inhibition of ribosomal RNA gene transcription during mitosis. J Cell Biol 129:561–575

    PubMed  CAS  Google Scholar 

  • Wu A, Tu X, Prisco M, Baserga R (2005) Regulation of upstream binding factor 1 activity by insulin-like growth factor I receptor signaling. J Biol Chem 280:2863–2872

    PubMed  CAS  Google Scholar 

  • Wullschleger S, Loewith R, Hall MN (2006) TOR signaling in growth and metabolism. Cell 124:471–484

    PubMed  CAS  Google Scholar 

  • Yamamoto K, Yamamoto M, Hanada K, Nogi Y, Matsuyama T, Muramatsu M (2004) Multiple protein-protein interactions by RNA polymerase I-associated factor PAF49 and role of PAF49 in rRNA transcription. Mol Cell Biol 24:6338–6340

    PubMed  CAS  Google Scholar 

  • Ye J, Zhao J, Hoffmann-Rohrer U, Grummt I (2008) Nuclear myosin I acts in concert with polymeric actin to drive RNA polymerase I transcription. Genes Dev 22:322–330

    PubMed  CAS  Google Scholar 

  • Yuan X, Zhao J, Zentgraf W, Hoffmann-Rohrer U, Grummt I (2002) Multiple interactions between RNA polymerase I, TIF-IA and TAF(I) subunits regulate preinitiation complex assembly at the ribosomal gene promoter. EMBO Rep 3:1082–1087

    PubMed  CAS  Google Scholar 

  • Yuan X, Zhou Y, Casanova E, Chai M, Kiss E, Gröne HJ, Schütz G, Grummt I (2005) Genetic inactivation of the transcription factor TIF-IA leads to nucleolar disruption, cell cycle arrest and p53-mediated apoptosis. Mol Cell 19:77–89

    PubMed  CAS  Google Scholar 

  • Zhang C, Comai L, Johnson DL (2005) PTEN represses RNA polymerase I transcription by disrupting the SL1 complex. Mol Cell Biol 25:6899–6911

    PubMed  CAS  Google Scholar 

  • Zhao J, Yuan X, Frödin M, Grummt I (2003) ERK-dependent phosphorylation of the transcription initiation factor TIF-IA is required for RNA polymerase I transcription and cell growth. Mol Cell 11:405–413

    PubMed  CAS  Google Scholar 

  • Zomerdijk JC, Beckmann H, Comai L, Tjian R (1994) Assembly of transcriptionally active RNA polymerase I initiation factor SL1 from recombinant subunits. Science 266:2015–2018

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Our work has been supported by grants from the Deutsche Forschungsge­meinschaft, the EU Network ‚The Epigenome’, the BMBF (‘EpiSys’), an ERC Advanced Grant, and the Fonds der Chemischen Industrie.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ingrid Grummt .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Voit, R., Grummt, I. (2011). The RNA Polymerase I Transcription Machinery. In: Olson, M. (eds) The Nucleolus. Protein Reviews, vol 15. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0514-6_6

Download citation

Publish with us

Policies and ethics