Case study- Mushroom poisoning ?

Case details

Two couples present to the emergency room with severe nausea, vomiting and diarrhea. One of the patients admits that she served salad at the dinner party to which she had added a few mushrooms she picked on a hike earlier. With such information, it is likely that their symptoms are a result of inhibition of which molecular event?

 A. Inhibition of RNA polymerase II

B. Inhibition of RNA polymerase I

C. Inhibition of RNA splicing

D. Inhibition of RNA Polyadenylation

E. Inhibition of RNA polymerase III

Answer- The correct answer is RNA polymerase II. It is a case of mushroom poisoning.

Alpha amanitin, from the mushroom Amanita phalloides mushroom, inhibits eukaryotic RNA polymerase II, the enzyme required for RNA synthesis. One single mushroom can very easily lead to a fast death in 10 days.

Alpha amanitin inhibits both the initiation and elongation states of transcription.

The other inhibitors of transcription are-

  • Rifampicin, that binds with Beta subunit of prokaryotic RNA polymerase,therefore, Rifampicin is a powerful drug for treatment of bacterial infections. It is used for the treatment of tuberculosis and leprosy.
  • Mitomycin- Intercalates with DNA strands and is used as an anticancer drug.
  • Actinomycin D- Intercalates with DNA strands (figure). Actinomycins inhibit both DNA and RNA synthesis by blocking chain elongation. They interact with G·C base pairs as they require the 2-amino group of guanine for binding. Actinomycins are used as anticancer drugs.

 

Actinomycin D

Figure- Actinomycins intercalate with DNA strands and inhibit the movement of RNA and DNA polymerases, thus they inhibit both replication as well as transcription.

As regards other options, RNA polymerase I is responsible for the synthesis of ribosomal RNA and RNA polymerase III is responsible for the synthesis of transfer RNA. They are not as sensitive to alpha amanitin as is RNA Polymerase II (Table).

Forms of RNA Polymerase Sensitivity to -Amanitin Major Products
I Insensitive rRNA
II High sensitivity mRNA, miRNAs
III Intermediate sensitivity tRNA/5S rRNA, snRNAs

RNA splicing is carried out by Small nuclear RNAs (SnRNAs).

RNA Polyadenylation is carried out by poly A polymerase. These processes are not inhibited by alpha amanitin.

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