Nutrient control of ribosomal gene expression (Saccharomyces cerevisiae)

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1, 2, 6, 9, 10, 14...3-5, 7, 8, 11...Transcription of5S RNA genestRNA genesRrn3pTFSfp1pTFAmino acidpermeasesMaf1pregulatorD-Glucoseamino acidsRNA Pol IISch9pkinaseGpr1preceptorTpk1pkinaseTpk3pkinaseRNA Pol IYak1pkinaseTorC1complexActiveSch9pkinaseActiveCrf1prepressorFhl1pregulatorIfh1pactivatorcAMPTpk2pkinaseRNA Pol IIICyr1padenylatecyclaseamino acidsMaf1pregulatorActiveMaf1pregulatorSfp1pTFActiveRrn3pTFActiveTorC1complexCrf1prepressorActivecytosolnucleusTranscription 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

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Bibliography

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  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
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History

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CompareRevisionActionTimeUserComment
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
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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
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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
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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
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78645view20:45, 12 January 2015StaciaSpecify description
78644view20:43, 12 January 2015StaciaSpecify description
78643view20:43, 12 January 2015StaciaPeriodical save, work in progress
78642view20:41, 12 January 2015StaciaSpecify description
78641view20:34, 12 January 2015StaciaSpecify description

External references

DataNodes

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NameTypeDatabase referenceComment
Amino acid permeases
Crf1p repressorProteinS000002631 (SGD)
Cyr1p

adenylate

cyclase		ProteinS000003542 (SGD)
D-GlucoseMetaboliteHMDB0000122 (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 complexComplexCPX-1715 (Complex Portal)
TorC1 complexComplexEBI-2435049 (IntAct)
Tpk1p kinaseProteinS000003700 (SGD)
Tpk2p kinaseProteinS000006124 (SGD)
Tpk3p kinaseProteinS000001649 (SGD)
Yak1p kinaseProteinS000003677 (SGD)
amino acidsMetaboliteCHEBI:33709 (ChEBI)
cAMPMetaboliteHMDB0000058 (HMDB)

Annotated Interactions

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