RNA polymerase action

The biochemical mode of action has been studied by several authors (16, 18). It appears that metalaxyl inhibits RNA synthesis by Interference with template-bound and a -amanitin-insensitive RNA polymerase action (15). 

DNA polymerase needs a primer on which to attach a new nucleotide unit for chain growth. Is a primer obligatory for RNA polymerase action ... 

A second major difference between prokaryotes and eukaryotes is the extent of RNA processing. Although both prokaryotes and eukaryotes modify tRNA and rRNA, eukaryotes very extensively process nascent RNA destined to become mRNA. Primary transcripts (pre-mRNA molecules), the products of RNA polymerase action, acquire a cap at... 

Chamberun, M. and Berg, P. (1964) Mechanism of RNA polymerase action formation of DNA-RNA hybrids with single-stranded templates. J. Molec. Biol. 8,297 characterization of the DNA-de-pendent synthesis of polyadenylic acid. Ibid., p. 708. 

The mode of action of the naphthoquinoid ansamacroHdes was estabHshed through studies using the tifamycins and streptovaricins (84,141,257,258). The ansamacroHdes inhibit bacterial growth by inhibiting RNA synthesis. This is accompHshed by forming a tight complex with DNA-dependent RNA polymerase. This complex is between the ansamacroHde and the P-unit of RNA polymerase. The formation of the complex inhibits the initation step of RNA synthesis (259,260). The ansamacroHdes form no such complex with mammalian RNA polymerase and thus have low mammalian toxicity. 

Thuringiensin (184), produced by B. thuringiensis (1,4) is a P-exotoxia that exerts its toxic action on insects and mammals through the inhibition of RNA polymerases. 

The sharp bend of DNA at the TATA box induced by TBP binding is favorable for the formation of the complete DNA control module in particular, for the interaction of specific transcription factors with TFIID. Since these factors may bind to DNA several hundred base pairs away from the TATA box, and at the same time may interact with TBP through one or several TAFs, there must be several protein-DNA interactions within this module that distort the regular B-DNA structure (see Figure 9.2). The DNA bend caused by the binding of TBP to the TATA box is one important step to bring activators near to the site of action of RNA polymerase. 

Phosphorylation of HSF substantially enhances the transcriptional activity of HS gene expression which may be up to 100-fold of basal levels after HSFl binds to the promoter element. Heat shock will increase the C-terminal-domain-kinase activity in cell extracts, and this action may enhance the activity of RNA polymerase II that is bound to HS genes (Legagneux et al., 1990). Whether this kinase activity also affects HSFl phosphorylation is not known, but increased HS gene expression appears to occur as long as HSFl is bound to the promoter region. The CTD kinase complex contains multiple proteins, and it is quite possible that one or more of these proteins is also regulated by stress. 

HCV drugs with a direct antiviral mode of action are needed for the treatment of chronic HCV infection. The NS3 protease, NS3 heficase (which localizes to the carboxy-terminal domain of NS3 and catalyzes the unwinding of the double stranded RNA in a 3 to 5 direction (Tai et al. 1996)), and NS5B RNA polymerase... 

Chromosome function Quinolones Metronidazole (also ) Nitrofu rantoin Rifampicin (also ) 5-Fluorocytosine Inhibit DNA gyrase DNA strand breakage DNA strand breakage Inhibits RNA polymerase Inhibits DNA synthesis No action on mammalian equivalent Requires anaerobic conditions not present in mammalian cells No action on mammalian equivalent Converted to active form in fungi... 

The action of rifampicin is upon the /3 subunit of RNA polymerase. Binding of just one molecule of rifampicin inhibits the initiation stage of transeription in whieh the first nucleotide is incorporated in the RNA ehain. Once started, transeription itself is not inhibited. It has been suggested that the stmeture of rifampiein resembles that of two adenosine nucleotides in RNA this may form the basis of the binding of the antibiotic to the j3 subunit. One problem is the rapid development of resistanee in organisms due... 

Cerklewski and Forbes 1976). Also, excess zinc protects zinc-containing enzymes like ALAS, ferrochelatase, and ALAD. In vivo, aqueous solution containing zinc administered to rats significantly reduced the genotoxic effects induced by lead (Kowalska-Wochna et al. 1988). It was postulated that zinc s protective action may be related to its functioning in DNA and RNA polymerases and consequent enhancement of cell repair processes. 

The mechanism of action of rifaximin depends on the inhibition of DNA-dependent RNA polymerase of the target microorganisms, leading to the suppression of initiation of chain formation in RNA synthesis. 

ACTIVATION OF TRANSCRIPTION by soluble hormones. The hormone is carried to its site of action by a carrier protein in the blood. The hormone crosses the membrane (by itself) and binds to a soluble receptor. A conformation change induced by hormone binding causes the receptor to expose its DNA binding site. This site binds to a specific sequence in the DNA upstream of genes that are to be activated for transcription. The transcription activation occurs through another domain of the protein that binds to components of the RNA polymerase complex. 

Drug X is an ami mycobacterial agent that inhibits other bacteria as well as poxviruses. However, it should not be used as a single agent because resistant mutants frequently form. The responsible mutation may alter the site of action of drug X [i.e., the deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase]. What is drug X ... 

Fig. 6.2. Proposed mechanisms of action of pure antiestrogens (fulvestrant). 1 Fulvestrant (ICI) binds to estrogen receptor (ER). 2 Fulvestrant binding to ER accelerates receptor degradation ( ER down-regulator ). 3 Rate of dimerization and nuclear localization of fulvestrant-ER complex is reduced. 4 Reduced binding of fulvestrant-ER to ERE. 5 No transcription of estrogen-responsive genes since AF-1 and AF-2 are inactive, no coactivators are recruited and the activity of RNA polymerase II is not activated (or inhibited) (Wakeling 2000)...

The counterpart of DNA polymerases in replication is RNA polymerases in transcription. Just as there are several DNA polymerases in vertebrate cells, so there are several RNA polymerases. To be precise, there are three of them. The different RNA polymerases are associated with three of the classes of RNA molecules found in vertebrate cells. Specifically, RNA polymerase I is responsible for the synthesis of the precursors of most rRNAs. RNA polymerase II plays the same role for the precursors of mRNA. Finally, RNA polymerase III is responsible for the synthesis of the precursors to the tRNAs as well as a few other small RNA molecules. Note here that I have specifically referred to precursors of these classes of RNA molecules. The initial products of the action of the RNA polymerases undergo further metabolism to yield the mature, functional products. 

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