Nutrient control of ribosomal gene expression (Saccharomyces cerevisiae)

From WikiPathways

Revision as of 18:33, 10 February 2015 by Stacia (Talk | contribs)
Jump to: navigation, search
3, 4, 7-9, 11...1, 2, 5, 6, 10...ActiveTranscription of5S RNA genestRNA genesRrn3pTFSfp1pTFAmino acidpermeasesMaf1pregulatorD-Glucoseamino acidsRNA Pol IISch9pkinaseGpr1preceptorTpk1pkinaseTpk3pkinaseRNA Pol IYak1pkinaseTorC1complexSch9pkinaseCrf1prepressorFhl1pregulatorIfh1pactivatorcAMPTpk2pkinaseRNA Pol IIICyr1padenylatecyclaseamino acidsMaf1pregulatorMaf1pregulatorActiveSfp1pTFRrn3pTFTorC1complexCrf1prepressorActiveActiveActiveActivecytosolnucleusTranscription ofribosomal protein genesribosome biogenesis genesTranscription ofrDNA genes


Description

Ribosomes are highly conserved large ribonucleoprotein (RNP) particles, consisting in yeast of a large 60S subunit and a small 40S subunit, that perform protein synthesis. Yeast ribosomes contain one copy each of four ribosomal RNAs (5S, 5.8S, 18S, and 25S; produced in two separate transcripts encoded within the rDNA repeat present as hundreds of copies on Chromosome 12) and 79 different ribosomal proteins (r-proteins), which are encoded by 137 different genes scattered about the genome, 59 of which are duplicated. The 60S subunit contains 46 proteins and three RNA molecules: 25S RNA of 3392 nt, hydrogen bonded to the 5.8S RNA of 158 nt and associated with the 5S RNA of 121 nt. The 40S subunit has a single 18S RNA of 1798 nt and 33 proteins. All yeast ribosomal proteins have a mammalian homolog.

PMID: 10690410, PMID: 22884264, PMID: 9421530, PMID: 9396790

In a rapidly growing yeast cell, 60% of total transcription is devoted to ribosomal RNA, and 50% of RNA polymerase II transcription and 90% of mRNA splicing are devoted to the production of mRNAs for r-proteins. Coordinate regulation of the rRNA genes and 137 r-protein genes is affected by nutritional cues and a number of signal transduction pathways that can abruptly induce or silence the ribosomal genes, whose transcripts have naturally short lifetimes, leading to major implications for the expression of other genes as well. The expression of some r-protein genes is influenced by Abf1p, and most are directly induced by binding of Rap1p to their promoters, which excludes nucleosomes and recruits Fhl1p and Ifh1p to drive transcription. PMID: 10409730, PMID: 12509467, PMID: 10542411, PMID: 2207166, PMID: 16782874

Ribosome synthesis is under nutrient control. Synthesis of the four rRNAs and 79 different proteins in equimolar amounts is one of the most energetically expensive cellular processes, and must be coordinated together. Ribosome biogenesis requires all three RNA polymerases: Pol I for rRNA genes, Pol II for ribosomal protein genes, and Pol III for tRNA and 5S RNA genes. Therefore, sensing quality and quantity of available nutrients is key in the regulation of ribosome biogenesis. PMID: 15489289, PMID: 18303986

Formation of transcription initiation complexes at the rDNA promoter depends on the association of RNA Pol I with the Rrn3p transcription factor, which is regulated by phosphorylation/dephosphorylation of Rrn3p. During normal conditions, a surface serine patch on Rrn3p is not phosphorylated, enabling it to bind RNA Pol I for efficient rDNA transcription. In stress conditions, the surface serine patch undergoes phosphorylation, which impairs the interaction of Rrn3p with RNA Pol I, repressing Pol I transcription, and thereby also reducing ribosome production and cell growth. The presence of glucose results in increased expression of RRN3. In cells treated with rapamycin, Rrn3p is subject to proteasome-dependent degradation, reducing the cellular amount of transcription-initiation competent RNA Pol I–Rrn3p complexes. PMID: 19796927, PMID: 8670901, PMID: 20421203, PMID: 20154141, PMID: 18084032, PMID: 11717393, PMID: 14595104

Ribosomal protein genes and ribosomal biogenesis genes are transcribed by RNA polymerase II. The activation of these promoters requires the forkhead-like transcription factor, Fhl1p, the acitvity of which is subject to nutrient regulation via the Ifh1 activator and the Crf1 repressor. Under lack of stress, the TorC1 complex retains Crf1p in the cytoplasm in a dephosphorylated, inactive state. Upon nutrient deprivation, the PKA-responsive Yak1 kinase phosphorylates Crf1p, resulting in its translocation to the nucleus, where Crf1p competes with the Ifh1 activator to bind Fhl1p. The transcription factor Sfp1p also mediates TorC1 regulation of ribosomal protein and ribosomal biogenesis genes. Interaction of Sfp1p with TorC1 reduces Sch9p phosphorylation, resulting in a negative feedback loop. PMID: 15620355, PMID: 19796927

Transcription by RNA polymerase III is negatively regulated by Maf1, a highly conserved repressor. Both the localization and activity of Maf1p are regulated by phosphorylation at various sites, mediated by TORC1, protein kinase A (PKA), and Sch9p. In its dephosphorylated state, Maf1p binds the N-terminus of the Rpc160p subunit of Pol III to prevent closed-complex formation. Maf1p is maintained in the cytoplasm during vegetative growth via PKA- or Sch9p-mediated phosphorylation. Dephosphorylation allows translocation of Maf1p to the nucleus and nucleolus under stress conditions, which shuts down RNA Pol III transcription.Phosphorylation of Maf1p by CK2 occurs at promoters, which releases Maf1p from chromatin, liberating RNA Pol III from inhibition. PMID: 19684113, PMID: 19299514, PMID: 21383183, PMID: 17005718, PMID: 22810236

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Mager WH, Planta RJ; ''Multifunctional DNA-binding proteins mediate concerted transcription activation of yeast ribosomal protein genes.''; Biochim Biophys Acta, 1990 PubMed Europe PMC Scholia
  2. Li B, Nierras CR, Warner JR; ''Transcriptional elements involved in the repression of ribosomal protein synthesis.''; Mol Cell Biol, 1999 PubMed Europe PMC Scholia
  3. Yamamoto RT, Nogi Y, Dodd JA, Nomura M; ''RRN3 gene of Saccharomyces cerevisiae encodes an essential RNA polymerase I transcription factor which interacts with the polymerase independently of DNA template.''; EMBO J, 1996 PubMed Europe PMC Scholia
  4. 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 PubMed Europe PMC Scholia
  5. Moir RD, Lee J, Willis IM; ''Recovery of RNA polymerase III transcription from the glycerol-repressed state: revisiting the role of protein kinase CK2 in Maf1 phosphoregulation.''; J Biol Chem, 2012 PubMed Europe PMC Scholia
  6. Mager WH, Planta RJ, Ballesta JG, Lee JC, Mizuta K, Suzuki K, Warner JR, Woolford J; ''A new nomenclature for the cytoplasmic ribosomal proteins of Saccharomyces cerevisiae.''; Nucleic Acids Res, 1997 PubMed Europe PMC Scholia
  7. Huber A, Bodenmiller B, Uotila A, Stahl M, Wanka S, Gerrits B, Aebersold R, Loewith R; ''Characterization of the rapamycin-sensitive phosphoproteome reveals that Sch9 is a central coordinator of protein synthesis.''; Genes Dev, 2009 PubMed Europe PMC Scholia
  8. Philippi A, Steinbauer R, Reiter A, Fath S, Leger-Silvestre I, Milkereit P, Griesenbeck J, Tschochner H; ''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 PubMed Europe PMC Scholia
  9. Zhao Y, McIntosh KB, Rudra D, Schawalder S, Shore D, Warner JR; ''Fine-structure analysis of ribosomal protein gene transcription.''; Mol Cell Biol, 2006 PubMed Europe PMC Scholia
  10. Rudra D, Warner JR; ''What better measure than ribosome synthesis?''; Genes Dev, 2004 PubMed Europe PMC Scholia
  11. Moir RD, Lee J, Haeusler RA, Desai N, Engelke DR, Willis IM; ''Protein kinase A regulates RNA polymerase III transcription through the nuclear localization of Maf1.''; Proc Natl Acad Sci U S A, 2006 PubMed Europe PMC Scholia
  12. Claypool JA, French SL, Johzuka K, Eliason K, Vu L, Dodd JA, Beyer AL, Nomura M; ''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 PubMed Europe PMC Scholia
  13. Goetze H, Wittner M, Hamperl S, Hondele M, Merz K, Stoeckl U, Griesenbeck J; ''Alternative chromatin structures of the 35S rRNA genes in Saccharomyces cerevisiae provide a molecular basis for the selective recruitment of RNA polymerases I and II.''; Mol Cell Biol, 2010 PubMed Europe PMC Scholia
  14. Zhao Y, Sohn JH, Warner JR; ''Autoregulation in the biosynthesis of ribosomes.''; Mol Cell Biol, 2003 PubMed Europe PMC Scholia
  15. Gerber J, Reiter A, Steinbauer R, Jakob S, Kuhn CD, Cramer P, Griesenbeck J, Milkereit P, Tschochner H; ''Site specific phosphorylation of yeast RNA polymerase I.''; Nucleic Acids Res, 2008 PubMed Europe PMC Scholia
  16. Conrad M, Schothorst J, Kankipati HN, Van Zeebroeck G, Rubio-Texeira M, Thevelein JM; ''Nutrient sensing and signaling in the yeast Saccharomyces cerevisiae.''; FEMS Microbiol Rev, 2014 PubMed Europe PMC Scholia
  17. Graczyk D, Debski J, Muszyńska G, Bretner M, Lefebvre O, Boguta M; ''Casein kinase II-mediated phosphorylation of general repressor Maf1 triggers RNA polymerase III activation.''; Proc Natl Acad Sci U S A, 2011 PubMed Europe PMC Scholia
  18. Verschoor A, Warner JR, Srivastava S, Grassucci RA, Frank J; ''Three-dimensional structure of the yeast ribosome.''; Nucleic Acids Res, 1998 PubMed Europe PMC Scholia
  19. Lee J, Moir RD, Willis IM; ''Regulation of RNA polymerase III transcription involves SCH9-dependent and SCH9-independent branches of the target of rapamycin (TOR) pathway.''; J Biol Chem, 2009 PubMed Europe PMC Scholia
  20. Zaman S, Lippman SI, Zhao X, Broach JR; ''How Saccharomyces responds to nutrients.''; Annu Rev Genet, 2008 PubMed Europe PMC Scholia
  21. Venema J, Tollervey D; ''Ribosome synthesis in Saccharomyces cerevisiae.''; Annu Rev Genet, 1999 PubMed Europe PMC Scholia
  22. Jenner L, Melnikov S, Garreau de Loubresse N, Ben-Shem A, Iskakova M, Urzhumtsev A, Meskauskas A, Dinman J, Yusupova G, Yusupov M; ''Crystal structure of the 80S yeast ribosome.''; Curr Opin Struct Biol, 2012 PubMed Europe PMC Scholia
  23. Lempiäinen H, Shore D; ''Growth control and ribosome biogenesis.''; Curr Opin Cell Biol, 2009 PubMed Europe PMC Scholia
  24. Warner JR; ''The economics of ribosome biosynthesis in yeast.''; Trends Biochem Sci, 1999 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
134113view11:08, 21 June 2024EgonwPermeases are proteins
134112view11:07, 21 June 2024EgonwAdded a missing identifier
110881view14:30, 17 June 2020EgonwReplaced an IntAct complex identifier with a Complex Portal identifier (the link out redirects to Complex Portal anyway)
107254view14:35, 17 September 2019MaintBotChEBI identifier normalization
107017view13:47, 17 September 2019MaintBotHMDB identifier normalization
89882view12:58, 6 October 2016MkutmonModified description
78912view20:25, 12 February 2015StaciaSpecify description
78870view18:33, 10 February 2015StaciaSpecify description
78762view13:12, 23 January 2015Bart SmeetsConnected all unconnected lines.
78761view13:08, 23 January 2015Bart SmeetsSpecify description
78760view13:07, 23 January 2015Bart SmeetsPeriodical save, work in progress
78759view12:57, 23 January 2015Bart SmeetsPeriodical save, work in progress
78703view18:04, 15 January 2015StaciaModified description
78702view17:54, 15 January 2015StaciaModified description
78688view05:56, 14 January 2015StaciaSpecify description
78687view05:51, 14 January 2015StaciaModified description
78686view05:32, 14 January 2015StaciaSpecify description
78685view05:29, 14 January 2015StaciaSpecify description
78678view00:35, 14 January 2015StaciaModified description
78677view00:34, 14 January 2015StaciaSpecify description
78676view00:32, 14 January 2015StaciaModified description
78675view00:00, 14 January 2015StaciaSpecify description
78674view23:53, 13 January 2015StaciaSpecify description
78673view23:50, 13 January 2015StaciaSpecify description
78672view23:23, 13 January 2015StaciaSpecify description
78669view00:04, 13 January 2015StaciaModified description
78668view00:04, 13 January 2015StaciaSpecify description
78667view00:03, 13 January 2015StaciaModified description
78666view23:54, 12 January 2015StaciaSpecify description
78665view23:50, 12 January 2015StaciaModified description
78664view23:16, 12 January 2015StaciaOntology Term : 'regulatory pathway' added !
78663view23:16, 12 January 2015StaciaOntology Term : 'signaling pathway' added !
78662view23:12, 12 January 2015StaciaSpecify description
78659view21:09, 12 January 2015StaciaSpecify description
78658view21:08, 12 January 2015StaciaSpecify description
78657view21:05, 12 January 2015StaciaSpecify description
78656view21:02, 12 January 2015StaciaSpecify description
78655view20:59, 12 January 2015StaciaSpecify description
78654view20:57, 12 January 2015StaciaSpecify description
78653view20:56, 12 January 2015StaciaSpecify description
78652view20:53, 12 January 2015StaciaPeriodical save, work in progress
78651view20:52, 12 January 2015StaciaSpecify description
78650view20:50, 12 January 2015StaciaSpecify description
78649view20:50, 12 January 2015StaciaSpecify description
78648view20:50, 12 January 2015StaciaSpecify description
78647view20:46, 12 January 2015StaciaSpecify description
78646view20:46, 12 January 2015StaciaSpecify description
78645view20:45, 12 January 2015StaciaSpecify description
78644view20:43, 12 January 2015StaciaSpecify description
78643view20:43, 12 January 2015StaciaPeriodical save, work in progress

External references

DataNodes

View all...
NameTypeDatabase referenceComment
Amino acid permeases
Crf1p repressorProteinS000002631 (SGD)
Cyr1p

adenylate

cyclase		ProteinS000003542 (SGD)
D-GlucoseMetaboliteHMDB00122 (HMDB)
Fhl1p regulatorProteinS000006308 (SGD)
Gpr1p receptorProteinS000002193 (SGD)
Ifh1p activatorProteinS000004213 (SGD)
Maf1p regulatorProteinS000002412 (SGD)
RNA Pol IComplexEBI-2339149 (IntAct)
RNA Pol IIIComplexS000005642 (SGD)
RNA Pol IIComplexS000002299 (SGD)
Rrn3p TFProteinS000001608 (SGD)
Sch9p kinaseProteinS000001248 (SGD)
Sfp1p TFProteinS000004395 (SGD)
TorC1 complexComplexEBI-2435049 (IntAct)
Tpk1p kinaseProteinS000003700 (SGD)
Tpk2p kinaseProteinS000006124 (SGD)
Tpk3p kinaseProteinS000001649 (SGD)
Yak1p kinaseProteinS000003677 (SGD)
amino acidsMetabolite33709 (ChEBI)
cAMPMetaboliteHMDB00058 (HMDB)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP2869"
Personal tools