Inhibitors of Multisubunit RNA Polymerases as Tools to Study Transcriptional Mechanisms in Prokaryotes and Eukaryotes

Small molecule inhibitors of multisubunit RNA polymerases (RNAP) have emerged as powerful tools for the study of transcriptional mechanisms in both prokaryotes and eukaryotes. Here, we review studies in which RNAP inhibitors such as α-amanitin, rifampicin and streptolydigin were used to reveal key molecular aspects of the transcription reaction and catalytic mechanisms of RNAP. Many of the most significant findings, that represent the main focus of this review, are related to the identification and characterization of RNAP mutants that confer resistance to inhibitors and crystallographic data of RNAP-inhibitor complexes. Understanding the mechanism of action of RNAP inhibitors may lead to the design of better drugs targeting bacterial and fungal infections as well as other human diseases such as cancer.