RNA polymerase synthesis

DNA-dependent enzyme synthesis is linear for 40-60 minutes (at 37°) in both the DEAE- and the preincubated S3 0-system (Gold and Schweiger, 1969 a Schweiger and Gold, 1969 a Zubay et al., 1970 a). Linearity, in this case, is a function of repeated reinitiations by RNA polymerases. Synthesis finally levels off as the substrates become limiting since by the addition of new substrates and fresh ribosomes, the synthesis can be restarted (unpublished). 

Herrlich, P., Schweiger, M. RNA polymerase synthesis in vitro directed by T7 phage DNA. Molec. gen. Genet. 110, 31-35 (1971a). 

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. 

Nebularine. Nebularine(44) is a naturaHy occurring purine riboside isolated from S.jokosukanensis (1,3,4). It is phosphorylated, and inhibits purine biosynthesis and RNA synthesis, but is not incorporated into RNA by E. coli RNA polymerase. It has also found appHcation as a transition state analogue for treatment of schistosomiasis and as a substrate for the restriction endonuclease, Hindll (138—141). 

Cro, by contrast, acts purely as a repressor. When it is bound to its high-affinity site at OR3, it prevents repressor synthesis by obstructing the access of polymerase to the left-hand promoter. In the absence of repressor, RNA polymerase can bind to the Cro promoter, and Cro can be synthesized along with the early phage genes to its right. 

The conversion of the information in DNA into proteins begins in the nucleus of cells with the synthesis of mRNA by transcription of DNA. In bacteria, the process begins when RNA polymerase recognizes and binds to a promoter... 

Although we will stick to the IL-6 gene, it should be mentioned at the side that two other RNA polymerases exist in mammalian cells responsible for the synthesis of RNA molecules, which are not translated into proteins ribosomal (rRNA), transfer (tRNA), small nuclear (snRNA), small nucleolar (snoRNA), and some of the recently discovered microRNAs and piRNAs. These RNA molecules act in the process of translation and mRNA turnover. Micro and piRNAs are probably extremely important in the definition of stem cells and of differentiation programs. Some of them are synthesized by RNA polymerase II. 

Figure 36-4. Illustration of the tight correlation between the presence of RNA polymerase II and RNA synthesis. A number of genes are activated when Chirono-mus tentans larvae are subjected to heat shock (39 °C for 30 minutes). A Distribution of RNA polymerase II (also called type B) in isolated chromosome IV from the salivary gland (at arrows). The enzyme was detected by immunofluorescence using an antibody directed against the polymerase. The 5C and BR3 are specific bands of chromosome IV, and the arrows indicate puffs. B Autoradiogram of a chromosome IV that was incubated in H-uridine to label the RNA. Note the correspondence of the immunofluorescence and presence of the radioactive RNA (black dots). Bar = 7 pm. (Reproduced, with permission, from Sass H RNA polymerase B in polytene chromosomes. Cell 1982 28 274. Copyright 1982 by the Massachusetts Institute of Technology.)...

With some RNA vimses, e.g. poliovims, the RNA strand fi cm the particle can act directly as mRNA and is translated into viral proteins on the host-cell ribosomes. In many other RNA vimses, however (e.g. the influenza vimses), the RNA strands are negative-sense RNAs (anhmessages) that have first to be transcribed to the complementary sequence by RNA-dependent RNA polymerases before they can function in protein synthesis. Sinee eukaryotie eells do not have these enzymes, the negative-sense RNA vimses must earry them in the virion. 

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... 

While metal-nitrogen and metal-oxygen bonded compounds dominate nucleobase coordination chemistry, examples in which metal-carbon bonds are formed have been identified. Early studies on the synthesis of metal-labeled DNA demonstrated that nucleotide-triphosphates, UTP, CTP, dUTP, and dCTP, can undergo mercury modification at C5 (82,83). The UTP derivative was also shown to act as a substrate for RNA polymerase in the presence of mercaptans (83). Later, guano-sine was shown to undergo mercury modification at C8 though, in this case, the purine was multiply substituted, 21 (84). 

Epirubicin inhibits both DNA and RNA polymerases and thus inhibits nucleic acid synthesis and topoisomerase II enzymes. Epirubicin pharmacokinetics are best described by a three-compartment model, with an a half-life of 4 to 5 minutes, a... 

E. coli RNA polymerase or Avian myetoblastosis DNA polymerase RNA or DNA synthesis NA + Hoffman and Niyogi 1977 Sirover and Loeb 1976... 

Virus messenger RNA In order for the new virus-specific proteins to be made from the virus genome, it is necessary for new virus-specific RNA molecules to be made. Exactly how the virus brings about new mRNA synthesis depends upon the type of virus, and especially upon whether its genetic material is RNA or DNA, and whether it is single-stranded or double-stranded. Which copy is read into mRNA depends upon the location of the appropriate promoter, since the promoter points the direction that the RNA polymerase will follow. In cells (uninfected with virus) all mRNA is made on the DNA template, but with RNA viruses the situation is obviously different. 

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