A child returns from a mushroom hunt in Northern Michigan begins vomiting and by the next morning is hospitalized with jaundice, hyperammonemia, and delirium. A toxicologist is called, who suggests poisoning from Amanita phylloides, a mushroom containing the toxin α-amanitin that inhibits RNA polymerase II. She suggests that the child’s liver failure is most likely due to which of the following?
1.Inhibition of ribosomal RNA synthesis
2.Inhibition of small RNA synthesis
3.Inhibition of tRNA and protein synthesis
4.Inhibition of mitochondrial RNA synthesis
5.Inhibition of mRNA synhesis
Three RNA polymerases are responsible for RNA transcription in Mammalian cells, RNA polymerase I for ribosomal RNA, RNA polymerase II for messenger RNA, and RNA polymerase III for transfer and small RNAs (5s, microRNAs). Mammalian RNA polymerase II is highly sensitive to the mushroom toxin α-amanitin, and even experienced mushroom gatherers can confuse the toxic Amanita species with edible varieties. Inhibition of RNA polymerase II-catalyzed HnRNA transcription seems to have the most dramatic effects in liver, perhaps because of its active role in protein synthesis. The liver damage caused by α-amanitin ingestion cannot be treated, requiring regeneration in milder ingestions and transplant in severe ones.