RNA Polymerase I Transcription (Homo sapiens)

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41535, 6, 10, 1729127, 1819814, 20, 2224244nucleoplasmGATAD2A CD3EAP ERCC3 HIST1H2BA Ac-TAF1B TAF1A HIST1H2BC TTF1UBTF TAF1D Me2K10-HIST1H3A CCNH TAF1C POLR2F TAF1CSal Box POLR2H HIST1H4 POLR2K RBBP7 TAF1A H2AFX NTPTTF1 POLR2EUBTF POLR1ErDNA Promoter H2AFB1 TAF1D POLR2LPOLR2L GTF2H1 TAF1C TAF1BH2AFZ CD3EAP p-UBTF ERCC3 TAF1D HIST2H2AC CD3EAP POLR1D HDAC2 TBP CHD4 HIST1H2BK MBD3 GTF2H4 CDK7 GTF2H1 nascent pre-rRNA transcript POLR2HMNAT1 TTF1 CD3EAP POLR1A HIST1H2BL POLR1E POLR2F TWISTNB p-UBTF TAF1C H2AFJ GTF2H2 Ac-TAF1B POLR2E TBP HIST1H2AD POLR2F POLR2L HIST1H2AB HIST1H2BO TAF1A POLR1D HIST1H2BC POLR2H H2AFV Acetylated SL1H2AFX HIST1H4 TWISTNB GTF2H4 EHMT2 POLR2F POLR2E HIST1H2AJ POLR2FH2AFJ POLR2L GTF2H5 POLR1B Ac-TAF1B TAF1D ADPMNAT1 HIST1H4 HIST1H2BC TAF1C TBPGTF2H3 GTF2H4 TAF1A CCNH MNAT1 TBP GTF2H1 TAF1A HIST1H2BB HIST1H2BD POLR1A POLR2E TAF1B HIST1H2BB CD3EAPPOLR1D HIST2H2BE PCAFGTF2H5 ZNRD1 TWISTNB HIST2H2AC Ac-TAF1B ZNRD1 TAF1C RNA Polymerase IHoloenzymeHIST1H2AJ POLR1Cp-UBTF HIST1H2BM rDNA Promoter ERCC6 HIST1H2BJ PTRFPOLR2E POLR1C POLR1C Me2K-10-H3F3A GTF2H1 POLR2K Me2K-10-HIST2H3A H3F3A POLR1E CDK7 PTRF HIST2H2BE Sal BoxHIST1H2BA RNA Polymerase ITranscriptionInitiation complexMTA1 TWISTNBHIST1H2BB H2BFS Me2K-10-HIST2H3A ERCC3 POLR1C POLR1E GTF2H3 KAT2B AcetylayedSL1:PhosUBF-1:rDNApromoterSal Box POLR2L HIST2H2AA3 POLR1B HIST1H2BH POLR1A rDNA Promoter POLR2K POLR1Anascent pre-rRNAtranscriptGATAD2B RRN3 p-T202, Y204 MAPK3dimerPOLR1B PTRF:PolymeraseI/Nascent Pre rRNAComplex:TTF-I:SalBoxPOLR1E HIST3H2BB POLR2L CoA-SHHIST1H2BN H2AFX TAF1D nascent pre-rRNA transcript HIST1H2AC POLR1A TWISTNB CCNH POLR2KPOLR1DATP HIST1H2BN DNA containing 5-mC POLR1B TTF1 CDK7 MNAT1 GTP HIST1H2BM elongating pre-rRNAtranscriptHIST1H2BK HIST1H2AD TTF-I:SalBox:CSB:G9a:NuRDTAF1D H2AFV UBTFHIST1H2BH GTF2H1 CD3EAP POLR2K TTF-I:Sal BoxPOLR2K POLR1D MTA2 RBBP4 ERCC2 Sal Box DNA HIST1H2AB GTF2H3 HIST1H2BD HIST1H2BL TWISTNB CDK7 HIST1H2BN HIST1H2BL ERCC2 TAF1C HIST1H2AC HIST1H3A ERCC3 UTP HIST1H2BJ CBX3 ERCC3 TAF1APOLR2H HIST1H2BO GTF2H3 GTF2H3 Chromatin (H3K9me2,5mC):MBD2GTF2H2 SL1HIST1H2BO POLR1E POLR1C CCNH HIST3H2BB TFIIHHIST1H2BM Me2K-10-H3F3A HIST1H2BD CD3EAP GTF2H2 GTF2H2 TBP CTP HIST1H2BH ERCC2 TAF1A CCNH H2BFS RNAPolymeraseI:rRNATranscript:TTF-1:Sal Box ComplexPOLR1A RNA Polymerase Ipromoter escapecomplexTTF1 ZNRD1 ZNRD1 GTF2H5 UBF-1:rDNA PromoterPOLR1E ZNRD1TBP ERCC2 HIST1H2AC TAF1DZNRD1 TAF1D GTF2H5 HIST1H2BJ POLR1C H2BFS MTA3 MBD2 POLR2H Active RNAPolymerase IPOLR2K GTF2H5 Ac-CoAMNAT1 Sal Box TWISTNB CDK7 RRN3Ac-TAF1B GTF2H2 POLR1BH2AFJ POLR2H KAT2A POLR1C PhosphorylatedUBF-1:rDNA promoterTAF1A UBTF HIST1H2BK HIST2H2AA3 UBTF TAF1C H2AFV POLR1B HIST1H2AD POLR1B H2AFZ H2AFB1 POLR1A H2AFB1 ATPrDNA Promoter GTF2H4 RRN3 HIST2H2AC POLR2H TBP HIST2H3A GTF2H4 POLR2F HIST3H2BB HIST2H2BE POLR1D HIST2H2AA3 HIST1H2AB TBP p-T202,Y204-MAPK3 POLR2F NucleosomeHIST1H2BA POLR2E H2AFZ ZNRD1 Me2K10-HIST1H3A CHD3 POLR2L POLR2E HDAC1 HIST1H2AJ rDNA PromoterChromatin(H3K9me2):CBX3ERCC2 Ac-TAF1B POLR1D 11, 13, 235, 6, 10, 17, 219161


Description

RNA polymerase (Pol) I (one of three eukaryotic nuclear RNA polymerases) is devoted to the transcription of the ribosomal DNA genes, which are found in multiple arrayed copies in every eukaryotic cell. These genes encode for the large ribosomal RNA precursor, which is then processed into the three largest subunits of the ribosomal RNA, the 18S, 28S, and 5.8S RNAs. In human cells the rDNA gene clusters are localized on the short arm of the five pairs of the acrocentric chromosomes. The rRNA promoter has two essential and specially spaced sequences: a CORE element and an upstream control element (UCE, also called UPE). The CORE element of the human promoter overlaps with the transcription start site, extending from 20 to 45, and is required for specific initiation of transcription.

The polymerase is a multisubunit complex, composed of two large subunits (the most conserved portions include the catalytic site that shares similarity with other eukaryotic and bacterial multisubunit RNA polymerases) and a number of smaller subunits. Under a number of experimental conditions the core is competent to mediate ribonucleic acid synthesis, in vivo however, it requires additional factors to select the appropriate template. In humans the RNA transcript (45S) is approximately 13,000 nucleotides long. Before leaving the nucleus as assembled ribosomal particles, the 45S rRNA is cleaved to give one copy each of the 28S rRNA, the 18S rRNA, and the 5.8S rRNA. Equal quantities of the three rRNAs are produced by initially transcribing them as one transcript.

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Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 73864
Reactome-version 
Reactome version: 74
Reactome Author 
Reactome Author: Comai, L

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Bibliography

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  1. Zhai W, Comai L.; ''Repression of RNA polymerase I transcription by the tumor suppressor p53.''; PubMed Europe PMC Scholia
  2. Schultz P, Fribourg S, Poterszman A, Mallouh V, Moras D, Egly JM.; ''Molecular structure of human TFIIH.''; PubMed Europe PMC Scholia
  3. Beckmann H, Chen JL, O'Brien T, Tjian R.; ''Coactivator and promoter-selective properties of RNA polymerase I TAFs.''; PubMed Europe PMC Scholia
  4. Comai L.; ''Mechanism of RNA polymerase I transcription.''; PubMed Europe PMC Scholia
  5. Gorski JJ, Pathak S, Panov K, Kasciukovic T, Panova T, Russell J, Zomerdijk JC.; ''A novel TBP-associated factor of SL1 functions in RNA polymerase I transcription.''; PubMed Europe PMC Scholia
  6. Jansa P, Mason SW, Hoffmann-Rohrer U, Grummt I.; ''Cloning and functional characterization of PTRF, a novel protein which induces dissociation of paused ternary transcription complexes.''; PubMed Europe PMC Scholia
  7. Hirschler-Laszkiewicz I, Cavanaugh AH, Mirza A, Lun M, Hu Q, Smink T, Rothblum LI.; ''Rrn3 becomes inactivated in the process of ribosomal DNA transcription.''; PubMed Europe PMC Scholia
  8. Ghoshal K, Majumder S, Datta J, Motiwala T, Bai S, Sharma SM, Frankel W, Jacob ST.; ''Role of human ribosomal RNA (rRNA) promoter methylation and of methyl-CpG-binding protein MBD2 in the suppression of rRNA gene expression.''; PubMed Europe PMC Scholia
  9. Rossignol M, Kolb-Cheynel I, Egly JM.; ''Substrate specificity of the cdk-activating kinase (CAK) is altered upon association with TFIIH.''; PubMed Europe PMC Scholia
  10. Giglia-Mari G, Giglia-Mari G, Coin F, Ranish JA, Hoogstraten D, Theil A, Wijgers N, Jaspers NG, Raams A, Argentini M, van der Spek PJ, Botta E, Stefanini M, Egly JM, Aebersold R, Hoeijmakers JH, Vermeulen W.; ''A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A.''; PubMed Europe PMC Scholia
  11. Tuan JC, Zhai W, Comai L.; ''Recruitment of TATA-binding protein-TAFI complex SL1 to the human ribosomal DNA promoter is mediated by the carboxy-terminal activation domain of upstream binding factor (UBF) and is regulated by UBF phosphorylation.''; PubMed Europe PMC Scholia
  12. Reiter A, Hamperl S, Seitz H, Merkl P, Perez-Fernandez J, Williams L, Gerber J, Németh A, Léger I, Gadal O, Milkereit P, Griesenbeck J, Tschochner H.; ''The Reb1-homologue Ydr026c/Nsi1 is required for efficient RNA polymerase I termination in yeast.''; PubMed Europe PMC Scholia
  13. Comai L, Tanese N, Tjian R.; ''The TATA-binding protein and associated factors are integral components of the RNA polymerase I transcription factor, SL1.''; PubMed Europe PMC Scholia
  14. Jantzen HM, Admon A, Bell SP, Tjian R.; ''Nucleolar transcription factor hUBF contains a DNA-binding motif with homology to HMG proteins.''; PubMed Europe PMC Scholia
  15. Bell SP, Pikaard CS, Reeder RH, Tjian R.; ''Molecular mechanisms governing species-specific transcription of ribosomal RNA.''; PubMed Europe PMC Scholia
  16. Russell J, Zomerdijk JC.; ''The RNA polymerase I transcription machinery.''; PubMed Europe PMC Scholia
  17. Pijnappel WP, Kolkman A, Baltissen MP, Heck AJ, Timmers HM.; ''Quantitative mass spectrometry of TATA binding protein-containing complexes and subunit phosphorylations during the cell cycle.''; PubMed Europe PMC Scholia
  18. Stefanovsky VY, Pelletier G, Hannan R, Gagnon-Kugler T, Rothblum LI, Moss T.; ''An immediate response of ribosomal transcription to growth factor stimulation in mammals is mediated by ERK phosphorylation of UBF.''; PubMed Europe PMC Scholia
  19. Comai L, Zomerdijk JC, Beckmann H, Zhou S, Admon A, Tjian R.; ''Reconstitution of transcription factor SL1: exclusive binding of TBP by SL1 or TFIID subunits.''; PubMed Europe PMC Scholia
  20. Pilsl M, Crucifix C, Papai G, Krupp F, Steinbauer R, Griesenbeck J, Milkereit P, Tschochner H, Schultz P.; ''Structure of the initiation-competent RNA polymerase I and its implication for transcription.''; PubMed Europe PMC Scholia
  21. Muth V, Nadaud S, Grummt I, Voit R.; ''Acetylation of TAF(I)68, a subunit of TIF-IB/SL1, activates RNA polymerase I transcription.''; PubMed Europe PMC Scholia
  22. Evers R, Grummt I.; ''Molecular coevolution of mammalian ribosomal gene terminator sequences and the transcription termination factor TTF-I.''; PubMed Europe PMC Scholia
  23. Engel C, Plitzko J, Cramer P.; ''RNA polymerase I-Rrn3 complex at 4.8 Å resolution.''; PubMed Europe PMC Scholia
  24. Yuan X, Zhao J, Zentgraf H, Hoffmann-Rohrer U, Grummt I.; ''Multiple interactions between RNA polymerase I, TIF-IA and TAF(I) subunits regulate preinitiation complex assembly at the ribosomal gene promoter.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
115046view16:58, 25 January 2021ReactomeTeamReactome version 75
113490view11:56, 2 November 2020ReactomeTeamReactome version 74
112690view16:08, 9 October 2020ReactomeTeamReactome version 73
101607view11:47, 1 November 2018ReactomeTeamreactome version 66
101144view21:33, 31 October 2018ReactomeTeamreactome version 65
100672view20:06, 31 October 2018ReactomeTeamreactome version 64
100222view16:51, 31 October 2018ReactomeTeamreactome version 63
99773view15:17, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99331view12:47, 31 October 2018ReactomeTeamreactome version 62
93416view11:23, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:456216 (ChEBI)
ATP MetaboliteCHEBI:30616 (ChEBI)
ATPMetaboliteCHEBI:30616 (ChEBI)
Ac-CoAMetaboliteCHEBI:15351 (ChEBI)
Ac-TAF1B ProteinQ53T94 (Uniprot-TrEMBL)
Acetylated SL1ComplexR-HSA-73693 (Reactome)
Acetylayed

SL1:PhosUBF-1:rDNA

promoter
ComplexR-HSA-73694 (Reactome)
Active RNA Polymerase IComplexR-HSA-73715 (Reactome)
CBX3 ProteinQ13185 (Uniprot-TrEMBL)
CCNH ProteinP51946 (Uniprot-TrEMBL)
CD3EAP ProteinO15446 (Uniprot-TrEMBL)
CD3EAPProteinO15446 (Uniprot-TrEMBL)
CDK7 ProteinP50613 (Uniprot-TrEMBL)
CHD3 ProteinQ12873 (Uniprot-TrEMBL)
CHD4 ProteinQ14839 (Uniprot-TrEMBL)
CTP MetaboliteCHEBI:17677 (ChEBI)
Chromatin (H3K9me2):CBX3ComplexR-HSA-427344 (Reactome)
Chromatin (H3K9me2, 5mC):MBD2ComplexR-HSA-427343 (Reactome)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
DNA R-ALL-29428 (Reactome)
DNA containing 5-mC R-ALL-212172 (Reactome)
EHMT2 ProteinQ96KQ7 (Uniprot-TrEMBL)
ERCC2 ProteinP18074 (Uniprot-TrEMBL)
ERCC3 ProteinP19447 (Uniprot-TrEMBL)
ERCC6 ProteinQ03468 (Uniprot-TrEMBL)
GATAD2A ProteinQ86YP4 (Uniprot-TrEMBL)
GATAD2B ProteinQ8WXI9 (Uniprot-TrEMBL)
GTF2H1 ProteinP32780 (Uniprot-TrEMBL)
GTF2H2 ProteinQ13888 (Uniprot-TrEMBL)
GTF2H3 ProteinQ13889 (Uniprot-TrEMBL)
GTF2H4 ProteinQ92759 (Uniprot-TrEMBL)
GTF2H5 ProteinQ6ZYL4 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
H2AFB1 ProteinP0C5Y9 (Uniprot-TrEMBL)
H2AFJ ProteinQ9BTM1 (Uniprot-TrEMBL)
H2AFV ProteinQ71UI9 (Uniprot-TrEMBL)
H2AFX ProteinP16104 (Uniprot-TrEMBL)
H2AFZ ProteinP0C0S5 (Uniprot-TrEMBL)
H2BFS ProteinP57053 (Uniprot-TrEMBL)
H3F3A ProteinP84243 (Uniprot-TrEMBL)
HDAC1 ProteinQ13547 (Uniprot-TrEMBL)
HDAC2 ProteinQ92769 (Uniprot-TrEMBL)
HIST1H2AB ProteinP04908 (Uniprot-TrEMBL)
HIST1H2AC ProteinQ93077 (Uniprot-TrEMBL)
HIST1H2AD ProteinP20671 (Uniprot-TrEMBL)
HIST1H2AJ ProteinQ99878 (Uniprot-TrEMBL)
HIST1H2BA ProteinQ96A08 (Uniprot-TrEMBL)
HIST1H2BB ProteinP33778 (Uniprot-TrEMBL)
HIST1H2BC ProteinP62807 (Uniprot-TrEMBL)
HIST1H2BD ProteinP58876 (Uniprot-TrEMBL)
HIST1H2BH ProteinQ93079 (Uniprot-TrEMBL)
HIST1H2BJ ProteinP06899 (Uniprot-TrEMBL)
HIST1H2BK ProteinO60814 (Uniprot-TrEMBL)
HIST1H2BL ProteinQ99880 (Uniprot-TrEMBL)
HIST1H2BM ProteinQ99879 (Uniprot-TrEMBL)
HIST1H2BN ProteinQ99877 (Uniprot-TrEMBL)
HIST1H2BO ProteinP23527 (Uniprot-TrEMBL)
HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
HIST1H4 ProteinP62805 (Uniprot-TrEMBL)
HIST2H2AA3 ProteinQ6FI13 (Uniprot-TrEMBL)
HIST2H2AC ProteinQ16777 (Uniprot-TrEMBL)
HIST2H2BE ProteinQ16778 (Uniprot-TrEMBL)
HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
HIST3H2BB ProteinQ8N257 (Uniprot-TrEMBL)
KAT2A ProteinQ92830 (Uniprot-TrEMBL)
KAT2B ProteinQ92831 (Uniprot-TrEMBL)
MBD2 ProteinQ9UBB5 (Uniprot-TrEMBL)
MBD3 ProteinO95983 (Uniprot-TrEMBL)
MNAT1 ProteinP51948 (Uniprot-TrEMBL)
MTA1 ProteinQ13330 (Uniprot-TrEMBL)
MTA2 ProteinO94776 (Uniprot-TrEMBL)
MTA3 ProteinQ9BTC8 (Uniprot-TrEMBL)
Me2K-10-H3F3A ProteinP84243 (Uniprot-TrEMBL)
Me2K-10-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
Me2K10-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
NTPComplexR-ALL-30595 (Reactome)
NucleosomeComplexR-HSA-427402 (Reactome)
PCAFComplexR-HSA-350078 (Reactome)
POLR1A ProteinO95602 (Uniprot-TrEMBL)
POLR1AProteinO95602 (Uniprot-TrEMBL)
POLR1B ProteinQ9H9Y6 (Uniprot-TrEMBL)
POLR1BProteinQ9H9Y6 (Uniprot-TrEMBL)
POLR1C ProteinO15160 (Uniprot-TrEMBL)
POLR1CProteinO15160 (Uniprot-TrEMBL)
POLR1D ProteinP0DPB5 (Uniprot-TrEMBL)
POLR1DProteinP0DPB5 (Uniprot-TrEMBL)
POLR1E ProteinQ9GZS1 (Uniprot-TrEMBL)
POLR1EProteinQ9GZS1 (Uniprot-TrEMBL)
POLR2E ProteinP19388 (Uniprot-TrEMBL)
POLR2EProteinP19388 (Uniprot-TrEMBL)
POLR2F ProteinP61218 (Uniprot-TrEMBL)
POLR2FProteinP61218 (Uniprot-TrEMBL)
POLR2H ProteinP52434 (Uniprot-TrEMBL)
POLR2HProteinP52434 (Uniprot-TrEMBL)
POLR2K ProteinP53803 (Uniprot-TrEMBL)
POLR2KProteinP53803 (Uniprot-TrEMBL)
POLR2L ProteinP62875 (Uniprot-TrEMBL)
POLR2LProteinP62875 (Uniprot-TrEMBL)
PTRF ProteinQ6NZI2 (Uniprot-TrEMBL)
PTRF:Polymerase

I/Nascent Pre rRNA Complex:TTF-I:Sal

Box
ComplexR-HSA-74982 (Reactome)
PTRFProteinQ6NZI2 (Uniprot-TrEMBL)
Phosphorylated UBF-1:rDNA promoterComplexR-HSA-73685 (Reactome)
RBBP4 ProteinQ09028 (Uniprot-TrEMBL)
RBBP7 ProteinQ16576 (Uniprot-TrEMBL)
RNA

Polymerase

I:rRNATranscript:TTF-1:Sal Box Complex
ComplexR-HSA-74979 (Reactome)
RNA Polymerase I HoloenzymeComplexR-HSA-73859 (Reactome)
RNA Polymerase I

Transcription

Initiation complex
ComplexR-HSA-73716 (Reactome)
RNA Polymerase I

promoter escape

complex
ComplexR-HSA-73717 (Reactome)
RRN3 ProteinQ9NYV6 (Uniprot-TrEMBL)
RRN3ProteinQ9NYV6 (Uniprot-TrEMBL)
SL1ComplexR-HSA-73692 (Reactome)
Sal Box ProteinU13369 (NCBI Protein) Named the "Sal Box" as a Sal I restriction endonuclease site is located within the sequence. An 18 base pair sequence element found in multiple copies in the nontranscribed spacer downstream of the 18S rRNA coding region. This element provides the termination signal for ribosomal gene transcription.
Sal BoxGeneProductU13369 (NCBI Protein) Named the "Sal Box" as a Sal I restriction endonuclease site is located within the sequence. An 18 base pair sequence element found in multiple copies in the nontranscribed spacer downstream of the 18S rRNA coding region. This element provides the termination signal for ribosomal gene transcription.
TAF1A ProteinQ15573 (Uniprot-TrEMBL)
TAF1AProteinQ15573 (Uniprot-TrEMBL)
TAF1B ProteinQ53T94 (Uniprot-TrEMBL)
TAF1BProteinQ53T94 (Uniprot-TrEMBL)
TAF1C ProteinQ15572 (Uniprot-TrEMBL)
TAF1CProteinQ15572 (Uniprot-TrEMBL)
TAF1D ProteinQ9H5J8 (Uniprot-TrEMBL)
TAF1DProteinQ9H5J8 (Uniprot-TrEMBL)
TBP ProteinP20226 (Uniprot-TrEMBL)
TBPProteinP20226 (Uniprot-TrEMBL)
TFIIHComplexR-HSA-109634 (Reactome)
TTF-I:Sal Box:CSB:G9a:NuRDComplexR-HSA-427352 (Reactome)
TTF-I:Sal BoxComplexR-HSA-74977 (Reactome)
TTF1 ProteinQ15361 (Uniprot-TrEMBL)
TTF1ProteinQ15361 (Uniprot-TrEMBL)
TWISTNB ProteinQ3B726 (Uniprot-TrEMBL)
TWISTNBProteinQ3B726 (Uniprot-TrEMBL)
UBF-1:rDNA PromoterComplexR-HSA-73684 (Reactome)
UBTF ProteinP17480 (Uniprot-TrEMBL)
UBTFProteinP17480 (Uniprot-TrEMBL)
UTP MetaboliteCHEBI:15713 (ChEBI)
ZNRD1 ProteinQ9P1U0 (Uniprot-TrEMBL)
ZNRD1ProteinQ9P1U0 (Uniprot-TrEMBL)
elongating pre-rRNA transcriptR-ALL-74985 (Reactome)
nascent pre-rRNA transcriptRnaNR_046235 (NCBI Protein)
nascent pre-rRNA transcript ProteinNR_046235 (NCBI Protein)
p-T202, Y204 MAPK3 dimerComplexR-HSA-109845 (Reactome)
p-T202,Y204-MAPK3 ProteinP27361 (Uniprot-TrEMBL)
p-UBTF ProteinP17480 (Uniprot-TrEMBL)
rDNA Promoter R-ALL-73682 (Reactome)
rDNA PromoterR-ALL-73682 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-73722 (Reactome)
ATPR-HSA-73722 (Reactome)
Ac-CoAR-HSA-73736 (Reactome)
Acetylated SL1ArrowR-HSA-73736 (Reactome)
Acetylated SL1R-HSA-73739 (Reactome)
Acetylayed

SL1:PhosUBF-1:rDNA

promoter
ArrowR-HSA-73739 (Reactome)
Acetylayed

SL1:PhosUBF-1:rDNA

promoter
R-HSA-73758 (Reactome)
Active RNA Polymerase IArrowR-HSA-73757 (Reactome)
Active RNA Polymerase IR-HSA-73758 (Reactome)
CD3EAPR-HSA-73865 (Reactome)
Chromatin (H3K9me2):CBX3ArrowR-HSA-74986 (Reactome)
Chromatin (H3K9me2, 5mC):MBD2TBarR-HSA-73718 (Reactome)
CoA-SHArrowR-HSA-73736 (Reactome)
NTPR-HSA-74986 (Reactome)
NucleosomeTBarR-HSA-73718 (Reactome)
PCAFmim-catalysisR-HSA-73736 (Reactome)
POLR1AR-HSA-73865 (Reactome)
POLR1BR-HSA-73865 (Reactome)
POLR1CR-HSA-73865 (Reactome)
POLR1DR-HSA-73865 (Reactome)
POLR1ER-HSA-73865 (Reactome)
POLR2ER-HSA-73865 (Reactome)
POLR2FR-HSA-73865 (Reactome)
POLR2HR-HSA-73865 (Reactome)
POLR2KR-HSA-73865 (Reactome)
POLR2LR-HSA-73865 (Reactome)
PTRF:Polymerase

I/Nascent Pre rRNA Complex:TTF-I:Sal

Box
ArrowR-HSA-74993 (Reactome)
PTRF:Polymerase

I/Nascent Pre rRNA Complex:TTF-I:Sal

Box
R-HSA-74992 (Reactome)
PTRFArrowR-HSA-74992 (Reactome)
PTRFR-HSA-74993 (Reactome)
Phosphorylated UBF-1:rDNA promoterArrowR-HSA-73722 (Reactome)
Phosphorylated UBF-1:rDNA promoterR-HSA-73739 (Reactome)
R-HSA-73718 (Reactome) UBF-1 binds directly to the CORE and UCE elements of the ribosomal DNA promoter. This binding is mediated by the HMG boxes (primarily HMG box1). Phosphorylation may play a role in the modulation of UBF's DNA binding activity, as well as in subsequent steps. UBF is thought to bind DNA in a conformation specific manner (as opposed to a sequence specific manner). The binding of UBF to the minor groove of DNA induces strong DNA bending.
R-HSA-73722 (Reactome) Phosphorylation of UBF-1, bound to the promoter, activates UBF-1 and recruits SL1, and eventually polymerase. This phosphorylation of UBF-1 by Erk1, has been shown to both weaken the binding of UBF-1 to DNA and to activate transcription (the authors of the paper showing these data suggest that loosening the binding of UBF-1 with the promoter may somehow promote transcription initiation). Though not definitively worked out phosphorylation of UBF-1 by Erk1 plays a role in the activation of the UBF-1:rDNA complex.
R-HSA-73729 (Reactome) Human SL1 is a four subunit complex composed of the TATA-binding protein (TBP) and three TBP-associated factors (TAFs): TAF(1)110, TAF(1)63, and TAF(1)48. Note that none of these three TAFs for Pol I show any homology to the Pol II or Pol III TAFs. TAFs SL1 is a species specific factor.
R-HSA-73736 (Reactome) Acetylation of the TAFI63 subunit of SL1 by PCAF stimulates the association of TAFI63 with DNA and stimulates pol I transcription in vitro. Conversely, deacetylation by the NAD+-dependent deacetylase Sir2 represses pol I transcription.
R-HSA-73739 (Reactome) Human SL1 does not bind to DNA itself, rather it is recruited to the rDNA promoter through a physical interaction with UBF-1. Phosphorylation of UBF-1 within the carboxy-terminal region is required for SL1 binding. SL1 consists of TATA-binding protein (TBP) and three associated factors (TAFIs). SL1 has no sequence-specific DNA binding activity its recruitment to the promoter being mediated by specific interactions with UBF. Once bound the SL1 complex makes direct contact with the DNA promoter and guides promoter-specific initiation.

Studies to identify the mechanistic relationship between SL1 and UBF-1 have indicated that the interaction between UBF-1 and SL1 is regulated by tumor suppressor proteins such as Rb and P53, although it has also been proposed that Rb prevents UBF-1 from binding to DNA itself.

R-HSA-73757 (Reactome) After the assembly of the RNA Polymerase I Holoenzyme, Rrn3 binding occurs (Engel et al. 2016, Pilsl et al. 2016).
R-HSA-73758 (Reactome) Composed of Acetylated SL1, phosphorylated UBF-1 bound the rDNA promoter as well as the active RNA polymerase holoenzyme, rrn3 and TFIIH the transcription initiation complex is complete. The assembly picture is incomplete, as the point at which TFIIH joins the complex is unknown, though by the time that this complex is formed TFIIH is present (it has been included at this step for completeness). This forms the transcriptionally active enzyme, that is capable of initiating transcription from the rDNA promoter.
R-HSA-73769 (Reactome) Upon transcription initiation it is thought that RRN3 is inactivated and dissociates from the Loss of Rrn3 from the RNA Polymerase I promoter escape complex. SL1 and UBF are thought to remain bound to the promoter for multiple rounds of transcription initiation
R-HSA-73865 (Reactome) At the beginning of this reaction, 1 molecule of each of POLR1A (RPA190, A194), POLR1B (RPA135), POLR1C (RPA40), POLR1D (RPA19), POLR1E (PAF53, RPA49), POLR2E (RPB5), POLR2F (RPB6), POLR2H (RPB8), POLR2K (RPABC4, RPB12), POLR2L (RPB10), TWISTNB (RPA43), CD3EAP (CAST, PAF49), and ZNRD1 (RPA12) are present. At the end of this reaction, 1 molecule of 'RNA Polymerase I Holoenzyme (Human)' is present.
This reaction takes place in the 'nucleolus'.

R-HSA-74986 (Reactome) At the beginning of this reaction, 1 molecule of 'elongating pre-rRNA transcript', and 1 molecule of 'NTP' are present. At the end of this reaction, 1 molecule of 'elongating pre-rRNA transcript' is present.

This reaction takes place in the 'nucleolus' and is mediated by the 'DNA-directed RNA polymerase activity' of 'RNA Polymerase I promoter escape complex'.

R-HSA-74987 (Reactome) As inferred from mouse cell models, the Transcription termination factor (TTF1, also known as TTF-1 and TTF-I) binds an 18 base pair sequence element known as the Sal Box found in multiple copies in the nontranscribed spacer downstream of the 28S rRNA coding region. This element is the termination signal for ribosomal gene transcription. Binding of TTF1 mediates the pausing of the elongating transcription complex. TTF1 has a relatively low affinity for purified DNA but binds cooperatively to chromatin. Oligomers of TTF1 interact in trans to bind adjacent intergenic regions and form loops of the rDNA. Binding of TTF1 to the Sal Box is also influenced by interaction of TTF1 with TIP5 and possibly other proteins.
R-HSA-74992 (Reactome) PTRF binds the quaternary complex and mediates the dissociation of paused complex. PTRF interacts with the RNA polymerase I largest subunit (p194), TTF-I and the U-rich 3' end of the nascent pre-rRNA.
R-HSA-74993 (Reactome) Dissociation of paused ternary complexes requires the Polymerase I-transcript release factor (PTRF) a leucine zipper protein. PTRF is capable of dissociating ternary Pol I transcription complexes, interacting with both TTF-I and Pol I to mediate the release of both Pol I and nascent transcripts from the template.
R-HSA-74994 (Reactome) The Polymerase I promoter escape complex/with the now complete nascent pre rRNA transcript pauses at the TTF-I bound Sal Box (Reiter et al.2012).
RNA

Polymerase

I:rRNATranscript:TTF-1:Sal Box Complex
ArrowR-HSA-74994 (Reactome)
RNA

Polymerase

I:rRNATranscript:TTF-1:Sal Box Complex
R-HSA-74993 (Reactome)
RNA Polymerase I HoloenzymeArrowR-HSA-73865 (Reactome)
RNA Polymerase I HoloenzymeR-HSA-73757 (Reactome)
RNA Polymerase I

Transcription

Initiation complex
ArrowR-HSA-73758 (Reactome)
RNA Polymerase I

Transcription

Initiation complex
R-HSA-73769 (Reactome)
RNA Polymerase I

promoter escape

complex
ArrowR-HSA-73769 (Reactome)
RNA Polymerase I

promoter escape

complex
ArrowR-HSA-74992 (Reactome)
RNA Polymerase I

promoter escape

complex
R-HSA-74994 (Reactome)
RNA Polymerase I

promoter escape

complex
mim-catalysisR-HSA-74986 (Reactome)
RRN3ArrowR-HSA-73769 (Reactome)
RRN3R-HSA-73757 (Reactome)
SL1ArrowR-HSA-73729 (Reactome)
SL1R-HSA-73736 (Reactome)
Sal BoxR-HSA-74987 (Reactome)
TAF1AR-HSA-73729 (Reactome)
TAF1BR-HSA-73729 (Reactome)
TAF1CR-HSA-73729 (Reactome)
TAF1DR-HSA-73729 (Reactome)
TBPR-HSA-73729 (Reactome)
TFIIHR-HSA-73758 (Reactome)
TTF-I:Sal Box:CSB:G9a:NuRDArrowR-HSA-73739 (Reactome)
TTF-I:Sal BoxArrowR-HSA-74987 (Reactome)
TTF-I:Sal BoxR-HSA-74994 (Reactome)
TTF1ArrowR-HSA-74992 (Reactome)
TTF1R-HSA-74987 (Reactome)
TWISTNBR-HSA-73865 (Reactome)
UBF-1:rDNA PromoterArrowR-HSA-73718 (Reactome)
UBF-1:rDNA PromoterR-HSA-73722 (Reactome)
UBTFR-HSA-73718 (Reactome)
ZNRD1R-HSA-73865 (Reactome)
elongating pre-rRNA transcriptArrowR-HSA-74986 (Reactome)
elongating pre-rRNA transcriptR-HSA-74986 (Reactome)
nascent pre-rRNA transcriptArrowR-HSA-74992 (Reactome)
nascent pre-rRNA transcriptR-HSA-74994 (Reactome)
p-T202, Y204 MAPK3 dimermim-catalysisR-HSA-73722 (Reactome)
rDNA PromoterR-HSA-73718 (Reactome)
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