2. α-amanitin inhibits
(1) only RNA polymerase I
(2) mainly RNA polymerase II
(3) only RNA polymerase III
(4) all RNA polymerases

Which RNA Polymerase Does α-Amanitin Inhibit? Detailed Explanation

Introduction

α-Amanitin is a deadly toxin derived from certain poisonous mushrooms, most notably the death cap (Amanita phalloides). Its notoriety in molecular biology comes from its highly selective inhibition of eukaryotic RNA polymerases, the enzymes responsible for synthesizing RNA from DNA templates. Understanding which RNA polymerase is most affected by α-amanitin is crucial for both exam preparation and laboratory research.

The Correct Answer

Among the options provided:

1. only RNA polymerase I

2. mainly RNA polymerase II

3. only RNA polymerase III

4. all RNA polymerases

The correct answer is (2): mainly RNA polymerase II.

How α-Amanitin Works

α-Amanitin binds specifically to the largest subunit of RNA polymerase II with high affinity, effectively blocking the enzyme’s ability to translocate along the DNA template during transcription. This inhibition is so potent that even very low concentrations can completely halt mRNA synthesis in eukaryotic cells.

Differential Sensitivity of RNA Polymerases

• RNA Polymerase II:
  This enzyme is highly sensitive to α-amanitin. It is responsible for synthesizing messenger RNA (mRNA) and some small nuclear RNAs. α-Amanitin binding blocks its function almost completely, even at low concentrations.

• RNA Polymerase III:
  This enzyme, which synthesizes tRNA and 5S rRNA, is moderately sensitive to α-amanitin. It is inhibited, but only at much higher concentrations compared to RNA polymerase II.

• RNA Polymerase I:
  This enzyme, which synthesizes most ribosomal RNA (rRNA), is resistant to α-amanitin and is not inhibited at concentrations that affect the other two polymerases.

Supporting Evidence

• Scientific studies confirm that α-amanitin is a highly selective inhibitor of RNA polymerase II, with only slight inhibitory effects on RNA polymerase III and no significant effect on RNA polymerase.

• Structural and biochemical analyses show that the toxin’s binding site is present and accessible in RNA polymerase II, explaining its high sensitivity.

Conclusion

α-Amanitin is a powerful and selective inhibitor of eukaryotic RNA polymerase II, with only minor effects on RNA polymerase III and no effect on RNA polymerase I at typical concentrations. This specificity is exploited in molecular biology research to distinguish between the activities of different RNA polymerases and is also the reason for the toxin’s severe effects in mushroom poisoning cases.