RNA/DNA Polymerase Inhibitors: Small Molecules and Peptides

RNA polymerases are categorized into two main groups: DNA-directed RNA polymerases (EC 2.7.7.6), commonly known as RNA polymerases or RNAP, which catalyze the synthesis of an RNA chain using a DNA template; and RNA-dependent RNA polymerases (EC 2.7.7.48), which catalyze the synthesis of an RNA chain from an RNA template.

In eukaryotes, four distinct forms of RNA polymerase (I-IV) exist, categorized based on the type of RNA they generate. RNA polymerase I (Pol I) is responsible for producing pre-ribosomal RNA (pre-rRNA 45S), constituting approximately 50% of the cell's RNA output. RNA polymerase II (Pol II) synthesizes precursors of mRNA , the majority of snRNA, and microRNA. RNA polymerase III (Pol III) generates tRNA, rRNA 5S, and various other small RNA within the cell. RNA polymerase IV is an enzyme in plants dedicated to producing small interfering RNA (siRNA). Viruses employ diverse DNA-directed RNA polymerases and RNA-dependent RNA polymerases.

DNA polymerases are the main enzymes for the synthesis of DNA from nucleoside triphosphates. In eukaryotes, fifteen distinct DNA polymerases has been identified. These enzymes play essential roles in both DNA replication and DNA repair processes. Some of these enzymes possess a distinctive 'proofreading' capability. DNA polymerases I, II, and III, for instance, exhibit 3' to 5' exonuclease activity, enabling them to eliminate incorrectly incorporated nucleotides. This intrinsic proofreading mechanism contributes to a remarkably low error rate during DNA replication, thereby preserving the integrity of the genome.