Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four mutants of Escherichia coli KL16 resistant to the antibiotic Thiolutin have been isolated. This drug was earlier reported to be an inhibitor of RNA chain elongation. The first mutant, TLrI, is resistant only in rich or partially rich media: it can, however, grow in minimal medium containing the drug with a very long doubling time. The other mutants TLrII, TLrIIIa and TLrIIIb are resistant in rich as well as minimal media. beta-galactosidase could not be induced in TLrI and TLrII in the presence of thiolutin whereas the enzyme is constitutively synthesised in TLrIIIa and TLrIIIb irrespective of the drug. The mutants do not support the development of phage T4 in presence of the drug, if the drug is added along with the phage, but "escape" the inhibition if phage development is allowed to proceed for some time before the addition of the drug. The time of this escape is characteristic of the mutant. Even in a sensitive strain, T7 growth escapes inhibition very soon after infection, around the time the phage-specific RNA polymerase is synthesized. In the parent strain the kinetics of inhibition of beta-galactosidase induction resembles more the inhibition caused by rifampicin than by streptolydigin. It is proposed that thiolutin could be an inhibitor of RNA chain initiation and resistance might be due to mutation in the subunit(s)/factor(s) involved in initiation.
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PMID:Thiolutin resistant mutants of Escherichia coli are they RNA chain initiation mutants? 77 14

We developed a procedure to measure mRNA decay rates in the yeast Saccharomyces cerevisiae and applied it to the determination of half-lives for 20 mRNAs encoded by well-characterized genes. The procedure utilizes Northern (RNA) or dot blotting to quantitate the levels of individual mRNAs after thermal inactivation of RNA polymerase II in an rpb1-1 temperature-sensitive mutant. We compared the results of this procedure with results obtained by two other procedures (approach to steady-state labeling and inhibition of transcription with Thiolutin) and also evaluated whether heat shock alter mRNA decay rates. We found that there are no significant differences in the mRNA decay rates measured in heat-shocked and non-heat-shocked cells and that, for most mRNAs, different procedures yield comparable relative decay rates. Of the 20 mRNAs studied, 11, including those encoded by HIS3, STE2, STE3, and MAT alpha 1, were unstable (t1/2 less than 7 min) and 4, including those encoded by ACT1 and PGK1, were stable (t1/2 greater than 25 min). We have begun to assess the basis and significance of such differences in the decay rates of these two classes of mRNA. Our results indicate that (i) stable and unstable mRNAs do not differ significantly in their poly(A) metabolism; (ii) deadenylation does not destabilize stable mRNAs; (iii) there is no correlation between mRNA decay rate and mRNA size; (iv) the degradation of both stable and unstable mRNAs depends on concomitant translational elongation; and (v) the percentage of rare codons present in most unstable mRNAs is significantly higher than in stable mRNAs.
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PMID:Identification and comparison of stable and unstable mRNAs in Saccharomyces cerevisiae. 218 28

Spontaneous mutants of Salmonella typhimurium isolated in our laboratory from thiolutin-containing tryptone agar plates are partially resistant to thiolutin in enriched media. In minimal media, they are not resistant. The mutants are not temperature sensitive but fail to support the development of phage P22 at higher temperatures (40 degrees C). Thiolutin did not interfere with RNA polymerase or nucleotide kinase in in vitro experiments. However, thiolutin did inhibit the rate of incorporation of exogenous uridine into the cellular pool and consequently the acid-precipitable material. It appears that one site of action of thiolutin is at the membrane level.
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PMID:Thiolutin-resistant mutants of Salmonella typhimurium. 675 84