| pubmed-article:18033801 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18033801 | lifeskim:mentions | umls-concept:C0036025 | lld:lifeskim |
| pubmed-article:18033801 | lifeskim:mentions | umls-concept:C0027950 | lld:lifeskim |
| pubmed-article:18033801 | lifeskim:mentions | umls-concept:C0032575 | lld:lifeskim |
| pubmed-article:18033801 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:18033801 | lifeskim:mentions | umls-concept:C0441889 | lld:lifeskim |
| pubmed-article:18033801 | lifeskim:mentions | umls-concept:C0018270 | lld:lifeskim |
| pubmed-article:18033801 | lifeskim:mentions | umls-concept:C1335439 | lld:lifeskim |
| pubmed-article:18033801 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:18033801 | lifeskim:mentions | umls-concept:C0205250 | lld:lifeskim |
| pubmed-article:18033801 | lifeskim:mentions | umls-concept:C1704666 | lld:lifeskim |
| pubmed-article:18033801 | lifeskim:mentions | umls-concept:C1517892 | lld:lifeskim |
| pubmed-article:18033801 | lifeskim:mentions | umls-concept:C0208973 | lld:lifeskim |
| pubmed-article:18033801 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:18033801 | pubmed:dateCreated | 2008-2-4 | lld:pubmed |
| pubmed-article:18033801 | pubmed:abstractText | To identify genes involved in poly(A) metabolism, we screened the yeast gene deletion collection for growth defects in the presence of cordycepin (3'-deoxyadenosine), a precursor to the RNA chain terminating ATP analog cordycepin triphosphate. Deltapho80 and Deltapho85 strains, which have a constitutively active phosphate-response pathway, were identified as cordycepin hypersensitive. We show that inorganic polyphosphate (poly P) accumulated in these strains and that poly P is a potent inhibitor of poly(A) polymerase activity in vitro. Binding analyses of poly P and yeast Pap1p revealed an interaction with a k(D) in the low nanomolar range. Poly P also bound mammalian poly(A) polymerase, however, with a 10-fold higher k(D) compared to yeast Pap1p. Genetic tests with double mutants of Deltapho80 and other genes involved in phosphate homeostasis and poly P accumulation suggest that poly P contributed to cordycepin hypersensitivity. Synergistic inhibition of mRNA synthesis through poly P-mediated inhibition of Pap1p and through cordycepin-mediated RNA chain termination may thus account for hypersensitive growth of Deltapho80 and Deltapho85 strains in the presence of the chain terminator. Consistent with this, a mutation in the 3'-end formation component rna14 was synthetic lethal in combination with Deltapho80. Based on these observations, we suggest that binding of poly P to poly(A) polymerase negatively regulates its activity. | lld:pubmed |
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| pubmed-article:18033801 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18033801 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18033801 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18033801 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:18033801 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18033801 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:18033801 | pubmed:issn | 1362-4962 | lld:pubmed |
| pubmed-article:18033801 | pubmed:author | pubmed-author:DichtlBernhar... | lld:pubmed |
| pubmed-article:18033801 | pubmed:author | pubmed-author:FreimoserFlor... | lld:pubmed |
| pubmed-article:18033801 | pubmed:author | pubmed-author:WernerThomas... | lld:pubmed |
| pubmed-article:18033801 | pubmed:author | pubmed-author:HolbeinSandra... | lld:pubmed |
| pubmed-article:18033801 | pubmed:author | pubmed-author:WengiAgnieszk... | lld:pubmed |
| pubmed-article:18033801 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18033801 | pubmed:volume | 36 | lld:pubmed |
| pubmed-article:18033801 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18033801 | pubmed:authorsComplete | Y | lld:pubmed |
