SIRT1 negatively regulates rRNA expression (Homo sapiens)

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1, 9, 104, 98, 949cytosolnucleoplasmNAMHIST1H2BD SL1HIST1H2BH HIST1H2BC HIST1H2BC HIST1H2BN HIST2H2AC HIST3H2BB HIST1H2BL HIST2H2AA3 H2AFJ HIST1H3A Ac-TAF1B SIRT1 HIST1H2BO HIST1H4 H2AFX HIST1H2BH 28S rRNA HIST1H2BJ HIST1H4 RRP8HIST1H2BO H2AFX HIST2H2BE H2AFV DNA HIST1H2BB 2xAcK-HIST2H3A H2AFB1 RRP8 H2AFZ HIST1H2BM DNA SUV39H1HIST1H2BA HIST1H2AJ HIST2H2BE H2BFS TAF1A 28S rRNA HIST1H2BN HIST1H2BC HIST1H2BA RRP8 HIST1H2BK SIRT1HIST1H2AJ H2AFZ NAD+2xAcK-HIST1H3A H2AFB1 HIST1H2BM HIST1H2AJ HIST2H2AC TAF1C H2AFJ HIST1H2BN 2xAcK-H3F3A TAF1A H2AFB1 HIST1H2AB TAF1D HIST2H3A HIST1H2BA H2AFZ HIST1H2AD DNA HIST1H2AJ HIST1H2BO HIST1H2AD HIST3H2BB DNA H2AFX Me2K10-HIST1H3A HIST2H2BE TAF1B Me2K10-HIST1H3A HIST1H2BL 5S rRNA HIST3H2BB ChromatinHIST1H4 HIST1H2BA H2AFV Acetylated SL1HIST3H2BB HIST1H2BC H3F3A HIST1H2AB 5.8S rRNA AdoHcyHIST1H2BL TBP HIST1H2AC HIST1H2BJ HIST2H2AC 5S RNA, 5.8S rRNA,28S rRNAHIST1H2BN HIST1H2BB RRP8:5S RNA, rRNAH2AFJ HIST1H2BK HIST1H2BH H2AFJ H2AFZ HIST2H2AA3 5.8S rRNA HIST1H2AD HIST1H2AB Chromatin withacetylated H3TAF1D Me2K-10-HIST2H3A HIST1H2BO HIST1H2BK eNoSCH2AFX HIST1H2BJ HIST1H2BM Me2K-10-HIST2H3A H2AFV 5S rRNA HIST1H2AC H2BFS HIST1H2BD HIST2H2AA3 2'-O-acetyl-ADP-riboseH2AFB1 HIST1H2BH Me2K-10-H3F3A Me2K-10-H3F3A HIST2H2BE HIST1H2BD HIST1H4 HIST1H2BK HIST1H2AB HIST1H2BJ HIST1H2AC H2BFS HIST1H2BM HIST2H2AC TBP H2BFS HIST1H2BL AdoMetHIST2H2AA3 HIST1H2AD TAF1C H2AFV HIST1H2AC HIST1H2BD HIST1H2BB HIST1H2BB Chromatin (H3K9me2)SUV39H1 2, 3, 5, 11, 1267944


Description

Expression of rRNA genes is coupled to the overall metabolism of the cell by the NAD-dependent histone deacetylase SIRT1, a component of the Energy-dependent Nucleolar Silencing Complex (eNoSC) (Murayama et al. 2008, reviewed in Salminen and Kaarniranta 2009, Grummt and Voit 2010). eNoSC comprises Nucleomethylin (NML), SIRT1, and the histone methylase SUV39H1 (Murayama et al. 2008). Deacetylation and methylation of histone H3 in the chromatin of a rRNA gene by eNoSC causes reduced expression of the gene. When glucose is low, NAD is high (NADH is low), activity of SIRT1 is high, and activity of rRNA genes is reduced. It is hypothesized that eNoSC forms on a nucleosome containing dimethylated lysine-9 on histone H3 (H3K9me2) and then eNoSC deacetylates and dimethylates the adjacent nucleosome, thus catalyzing spreading of H3K9me2 throughout the gene. View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 427359
Reactome-version 
Reactome version: 74
Reactome Author 
Reactome Author: May, Bruce

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Bibliography

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  1. Grummt I, Voit R.; ''Linking rDNA transcription to the cellular energy supply.''; PubMed Europe PMC Scholia
  2. 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
  3. 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
  4. Yang L, Song T, Chen L, Kabra N, Zheng H, Koomen J, Seto E, Chen J.; ''Regulation of SirT1-nucleomethylin binding by rRNA coordinates ribosome biogenesis with nutrient availability.''; PubMed Europe PMC Scholia
  5. 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
  6. 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
  7. Jackson MD, Denu JM.; ''Structural identification of 2'- and 3'-O-acetyl-ADP-ribose as novel metabolites derived from the Sir2 family of beta -NAD+-dependent histone/protein deacetylases.''; PubMed Europe PMC Scholia
  8. Vaquero A, Scher M, Lee D, Erdjument-Bromage H, Tempst P, Reinberg D.; ''Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin.''; PubMed Europe PMC Scholia
  9. Murayama A, Ohmori K, Fujimura A, Minami H, Yasuzawa-Tanaka K, Kuroda T, Oie S, Daitoku H, Okuwaki M, Nagata K, Fukamizu A, Kimura K, Shimizu T, Yanagisawa J.; ''Epigenetic control of rDNA loci in response to intracellular energy status.''; PubMed Europe PMC Scholia
  10. Salminen A, Kaarniranta K.; ''SIRT1 regulates the ribosomal DNA locus: epigenetic candles twinkle longevity in the Christmas tree.''; PubMed Europe PMC Scholia
  11. 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
  12. Bell SP, Pikaard CS, Reeder RH, Tjian R.; ''Molecular mechanisms governing species-specific transcription of ribosomal RNA.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
113351view11:42, 2 November 2020ReactomeTeamReactome version 74
112560view15:52, 9 October 2020ReactomeTeamReactome version 73
101473view11:33, 1 November 2018ReactomeTeamreactome version 66
101011view21:13, 31 October 2018ReactomeTeamreactome version 65
100547view19:47, 31 October 2018ReactomeTeamreactome version 64
100095view16:32, 31 October 2018ReactomeTeamreactome version 63
99645view15:03, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99247view12:44, 31 October 2018ReactomeTeamreactome version 62
93928view13:45, 16 August 2017ReactomeTeamreactome version 61
93514view11:25, 9 August 2017ReactomeTeamreactome version 61
88423view11:57, 5 August 2016FehrhartOntology Term : 'regulatory pathway' added !
86611view09:22, 11 July 2016ReactomeTeamreactome version 56
83355view10:56, 18 November 2015ReactomeTeamVersion54
81515view13:03, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
2'-O-acetyl-ADP-riboseMetaboliteCHEBI:76279 (ChEBI)
28S rRNA ProteinM11167 (EMBL)
2xAcK-H3F3A ProteinP84243 (Uniprot-TrEMBL)
2xAcK-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
2xAcK-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
5.8S rRNA ProteinJ01866 (EMBL)
5S RNA, 5.8S rRNA, 28S rRNAComplexR-HSA-5096484 (Reactome)
5S rRNA ProteinV00589 (EMBL)
Ac-TAF1B ProteinQ53T94 (Uniprot-TrEMBL)
Acetylated SL1ComplexR-HSA-73693 (Reactome)
AdoHcyMetaboliteCHEBI:16680 (ChEBI)
AdoMetMetaboliteCHEBI:15414 (ChEBI)
Chromatin (H3K9me2)ComplexR-HSA-3211683 (Reactome)
Chromatin with acetylated H3ComplexR-HSA-3211727 (Reactome)
ChromatinComplexR-HSA-3211736 (Reactome)
DNA R-ALL-29428 (Reactome)
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)
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)
Me2K-10-H3F3A ProteinP84243 (Uniprot-TrEMBL)
Me2K-10-HIST2H3A ProteinQ71DI3 (Uniprot-TrEMBL)
Me2K10-HIST1H3A ProteinP68431 (Uniprot-TrEMBL)
NAD+MetaboliteCHEBI:57540 (ChEBI)
NAMMetaboliteCHEBI:17154 (ChEBI)
RRP8 ProteinO43159 (Uniprot-TrEMBL)
RRP8:5S RNA, rRNAComplexR-HSA-5096496 (Reactome)
RRP8ProteinO43159 (Uniprot-TrEMBL)
SIRT1 ProteinQ96EB6 (Uniprot-TrEMBL)
SIRT1ProteinQ96EB6 (Uniprot-TrEMBL)
SL1ComplexR-HSA-73692 (Reactome)
SUV39H1 ProteinO43463 (Uniprot-TrEMBL)
SUV39H1ProteinO43463 (Uniprot-TrEMBL)
TAF1A ProteinQ15573 (Uniprot-TrEMBL)
TAF1B ProteinQ53T94 (Uniprot-TrEMBL)
TAF1C ProteinQ15572 (Uniprot-TrEMBL)
TAF1D ProteinQ9H5J8 (Uniprot-TrEMBL)
TBP ProteinP20226 (Uniprot-TrEMBL)
eNoSCComplexR-HSA-427510 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
2'-O-acetyl-ADP-riboseArrowR-HSA-427514 (Reactome)
2'-O-acetyl-ADP-riboseArrowR-HSA-5211239 (Reactome)
5S RNA, 5.8S rRNA, 28S rRNAR-HSA-5096488 (Reactome)
5S RNA, 5.8S rRNA, 28S rRNATBarR-HSA-427528 (Reactome)
Acetylated SL1R-HSA-5211239 (Reactome)
AdoHcyArrowR-HSA-427527 (Reactome)
AdoMetR-HSA-427527 (Reactome)
Chromatin (H3K9me2)ArrowR-HSA-427527 (Reactome)
Chromatin (H3K9me2)R-HSA-427528 (Reactome)
Chromatin with acetylated H3R-HSA-427514 (Reactome)
ChromatinArrowR-HSA-427514 (Reactome)
ChromatinR-HSA-427527 (Reactome)
NAD+R-HSA-427514 (Reactome)
NAD+R-HSA-5211239 (Reactome)
NAMArrowR-HSA-427514 (Reactome)
NAMArrowR-HSA-5211239 (Reactome)
R-HSA-427514 (Reactome) The Sirtuin-1 (SIRT1) component of eNoSC deacetylates histone H3 at lysine-9 (Vaquero et al. 2004, Murayama et al. 2008). The reaction uses nicotinamide adenine dinucleotide (NAD) as the acceptor of the acetyl group and generates nicotinamide and 1-O-acetyl-ADP-ribose as products (Vaquero et al. 2004). The use of NAD links the reaction to the overall energy balance of the cell. Cells exposed to high glucose have a greater NADH:NAD ratio and therefore lower activity of eNoSC (Murayama et al. 2008). Low glucose produces higher NAD and higher activity of eNoSC.
R-HSA-427527 (Reactome) The SUV39H1 component of eNoSC dimethylates histone H3 at lysine-9 (Murayama et al. 2008). The reaction depends on the prior deacetylation reaction catalyzed by the SIRT1 component of eNoSC. Histone H3 dimethylated at lysine-9 inhibits expression of rRNA genes.
R-HSA-427528 (Reactome) RRP8 (Nucleomethylin, NML), SIRT1, and SUV39H1 form the energy-dependent Nucleolar Silencing Complex (eNoSC) at inactive rRNA genes (Murayama et al. 2008). RRP8 is constitutively located in the nucleolus (Yang et al. 2013), binds histone H3 dimethylated at lysine-9 (Murayama et al. 2008) and appears to recruit SIRT1 from the nucleoplasm to the nucleolus (Yang et al. 2013). The eNoSC binds chromatin throughout the rRNA transcription unit. SIRT1 may deacetylate and, hence, activate SUV39H1 but this has not yet been shown at rDNA. Abrogation of any member of eNoSC interferes with binding of the other members of the complex. The eNoSC complex appears to cause spreading of heterochromatin at rDNA.
R-HSA-5096488 (Reactome) RRP8 (Nucleomethylin, NML) recruits SIRT1 to the nucleolus to form the energy-dependent Nucleolar Silencing Complex (eNoSC), which induces chromatin changes that inhibit rRNA transcription. RRP8 can bind 5S RNA (transcribed by RNA ploymerase III), 5.8S rRNA, and 28S rRNA and the bound RNA prevents RRP8 from binding SIRT1 (Yang et al. 2013). Thus the level of 5S RNA, 5.8S rRNA, and 28S rRNA in the nucleus negatively regulates the assembly of eNoSC, coupling transcriptional regulation of rRNA to epigenetic silencing of rRNA genes.
R-HSA-5211239 (Reactome) As inferred from mouse, SIRT1, an NAD+ dependent deacetylase, deacetylates the TAF1B (TAF(1)68) subunit of the SL1 complex. Deacetylation of TAF1B inhibits transcription of rRNA genes.
RRP8:5S RNA, rRNAArrowR-HSA-5096488 (Reactome)
RRP8R-HSA-427528 (Reactome)
RRP8R-HSA-5096488 (Reactome)
SIRT1R-HSA-427528 (Reactome)
SIRT1mim-catalysisR-HSA-5211239 (Reactome)
SL1ArrowR-HSA-5211239 (Reactome)
SUV39H1R-HSA-427528 (Reactome)
eNoSCArrowR-HSA-427528 (Reactome)
eNoSCmim-catalysisR-HSA-427514 (Reactome)
eNoSCmim-catalysisR-HSA-427527 (Reactome)
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