Introduction
Transfer of nucleotide language of DNA to the nucleotide language of RNA, with the replacement of T by U. The process has been catalyzed by the enzyme DNA dependent RNA polymerase.
INHIBITORS OF RNA SYNTHESIS
RNA synthesis(Transcription) involved in three steps Viz Chain initiation, Chain elongation and Termination. Inhibitors of RNA synthesis can acts on only DNA and RNA polymerase.
Inhibitors of RNA synthesis mainly categorized into two types based on the compound involved in RNA synthesis:-
Type 1: Inhibitors interact with DNA dependent RNA polymerase and inhibit the RNA synthesis.
Type 2: Inhibitors interact with DNA(Deoxyribonucleic acid) and inhibit the RNA synthesis.
Type 1: Inhibitors interact with DNA dependent RNA polymerase and inhibit the RNA synthesis. The enzyme which transcribe DNA synthesizing RNA(DNA dependent RNA polymerase) have structural differences in eukaryotic and prokaryotic cells
In Eukaryotic cells(a-amanitin)
1. a-amanitin
It is a highly toxic, cyclic octopeptide , isolated from poisonus fungus Amanita phalloides (Mushrooms)
It is a member of Amatoxin. Mechanism behind this antibiotic is formation of multiple stereospecific hydrogen bonds. a-amanitin interacts with bridge helix in RNA polymerase 2. The addition of a-amanitin can reduce the rate of RNA polymerase, Transcribing on DNA from several thousands to few nucleotides per minute. Binding of a-amanitin puts a constraint on its mobility, hence slowing down the translocation of the polymerase and the rate of synthesis of the RNA molecule It occurs in elongation process of transcription
2.Rifamycin
It is a inhibitor of RNA polymerase, specifically inhibits the initiation step of RNA synthesis and it is also called potent inhibitor of chain initiation. Chain elongation in the transcription reaction is not affected by this antibiotic, but a step of initiation are inhibited.
Type 2: Inhibitors interact with DNA(Deoxy ribonucleic acid) and inhibit the RNA synthesis.
Below are the antibiotics interact with DNA and inhibit the RNA synthesis:-
1. Actinomycin D
Actinomycin D is the most significant member of actinomycines, which are a class of polypeptide antitumor antibiotics isolated from soil bacteria of the genus streptomyces. Actinomycin D is chromopeptide with antibiotic activity. It binds specifically to the minor groove of the DNA double helix, and thus prevents it from being a template for RNA synthesis. Its ability to inhibit growth of rapid dividing cells makes it a effective agent in cancer treatment.
2.Chromomycin A3
Chromomycin A3 is the Anthraquinone antibiotic. It is soluble in ethanol and DMSO(dimethylsulfoxide). Chromomycin A3 binds to transcription factor SP1& SP3 of DNA to inhibit RNA synthesis.