| http://purl.uniprot.org/citations/25815716 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25815716 | http://www.w3.org/2000/01/rdf-schema#comment | "Ribosomal RNA synthesis is controlled by nutrient signaling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. mTORC1 regulates ribosomal RNA expression by affecting RNA Polymerase I (Pol I)-dependent transcription of the ribosomal DNA (rDNA) but the mechanisms involved remain obscure. This study provides evidence that the Ccr4-Not complex, which regulates RNA Polymerase II (Pol II) transcription, also functions downstream of mTORC1 to control Pol I activity. Ccr4-Not localizes to the rDNA and physically associates with the Pol I holoenzyme while Ccr4-Not disruption perturbs rDNA binding of multiple Pol I transcriptional regulators including core factor, the high mobility group protein Hmo1, and the SSU processome. Under nutrient rich conditions, Ccr4-Not suppresses Pol I initiation by regulating interactions with the essential transcription factor Rrn3. Additionally, Ccr4-Not disruption prevents reduced Pol I transcription when mTORC1 is inhibited suggesting Ccr4-Not bridges mTORC1 signaling with Pol I regulation. Analysis of the non-essential Pol I subunits demonstrated that the A34.5 subunit promotes, while the A12.2 and A14 subunits repress, Ccr4-Not interactions with Pol I. Furthermore, ccr4Δ is synthetically sick when paired with rpa12Δ and the double mutant has enhanced sensitivity to transcription elongation inhibition suggesting that Ccr4-Not functions to promote Pol I elongation. Intriguingly, while low concentrations of mTORC1 inhibitors completely inhibit growth of ccr4Δ, a ccr4Δ rpa12Δ rescues this growth defect suggesting that the sensitivity of Ccr4-Not mutants to mTORC1 inhibition is at least partially due to Pol I deregulation. Collectively, these data demonstrate a novel role for Ccr4-Not in Pol I transcriptional regulation that is required for bridging mTORC1 signaling to ribosomal RNA synthesis."xsd:string |
| http://purl.uniprot.org/citations/25815716 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pgen.1005113"xsd:string |
| http://purl.uniprot.org/citations/25815716 | http://purl.uniprot.org/core/author | "Chen H."xsd:string |
| http://purl.uniprot.org/citations/25815716 | http://purl.uniprot.org/core/author | "Laribee R.N."xsd:string |
| http://purl.uniprot.org/citations/25815716 | http://purl.uniprot.org/core/author | "Workman J.J."xsd:string |
| http://purl.uniprot.org/citations/25815716 | http://purl.uniprot.org/core/author | "Hosni-Ahmed A."xsd:string |
| http://purl.uniprot.org/citations/25815716 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25815716 | http://purl.uniprot.org/core/name | "PLoS Genet"xsd:string |
| http://purl.uniprot.org/citations/25815716 | http://purl.uniprot.org/core/pages | "e1005113"xsd:string |
| http://purl.uniprot.org/citations/25815716 | http://purl.uniprot.org/core/title | "Ccr4-not regulates RNA polymerase I transcription and couples nutrient signaling to the control of ribosomal RNA biogenesis."xsd:string |
| http://purl.uniprot.org/citations/25815716 | http://purl.uniprot.org/core/volume | "11"xsd:string |
| http://purl.uniprot.org/citations/25815716 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25815716 |
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