Medical Perspectives: Transcription

As was the case for DNA replication, you are not going get a visit from a patient with any inborn defect in the general machinery of transcription. However, every spring and summer a few patients, usually in California, come in suffering from a system-wide shut down of eukaryotic PolII RNA polymerase. The primary symptoms are due to liver failure. They are suffering from alpha-amanitin poisoning. The toxin is produced by several of the amanitas mushrooms, notably Amanita phalloides (Death Cap) and Amanita ocreata (Destroying Angel). On the plus side, they taste really good! The closely related Amanita velosa (Spring Amanita), is also very tasty - and harmless. You really need to have faith in your taxonomy before you go picking those. So, if PolII has been inhibited system-wide - why are the symptoms largely those of liver failure?

There is also one family of antibiotics that work by preferentially inhibiting prokaryotic RNA polymerase. The original was isolated from an actinomycete bacteria, but collectively the derivatives (Rifampin aka Rifampicin, rifabutin, rifapentine, rifaximin) are known as rifamycins. They exhibit potent activity against pathogenic Gram-positive cocci and mycobacteria. While resistant bacteria can develop, via mutations in their RNA polymerase gene, this usually cannot be horizontally transferred from one bacteria to another.