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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# RNA polymerases I, II and III

RNA polymerases copy DNA into RNA; human cells have three in the nucleus, each dedicated to a type of RNA.

Updated 2026-11-01

Loading the 3D model…

## Key facts

- Pol I (nucleolus): the 45S precursor of 28S, 18S and 5.8S rRNA.
- Pol II (nucleoplasm): mRNA and most snRNAs and microRNAs. Most sensitive to α-amanitin.
- Pol III: tRNA, 5S rRNA, U6 snRNA and other small RNAs. Intermediate α-amanitin sensitivity; Pol I is resistant.
- They synthesise 5'→3' without a primer and without proofreading (more errors than DNA polymerase, but not inherited).
- Mitochondria have their own single-subunit RNA polymerase (POLRMT).

**Also called**
Pol I, Pol II, Pol III

**EC number**
[2.7.7.6](https://www.enzyme-database.org/query.php?ec=2.7.7.6)

**Genes**
POLR1A, POLR2A, POLR3A (and the other subunits)

**Structure (PDB)**
[8WB0](https://www.rcsb.org/structure/8WB0)

## Regulation

- Pol II depends on general factors (TFIID/TBP, TFIIB, TFIIH…), Mediator and activators on enhancers.
- Phosphorylation of the RPB1 CTD (YSPTSPS repeats): serine 5 at initiation, serine 2 during elongation.
- Pol I and Pol III output rises with growth signals (mTOR, MYC) to build ribosomes.

## Inhibitors and toxins

- α-amanitin (Pol II > Pol III; Amanita mushrooms)
- Actinomycin D (intercalator; mostly stalls Pol I)
- Rifampicin (bacterial RNA polymerase only)
- Fidaxomicin (Clostridioides difficile RNA polymerase)

## Clinical notes

- Amanita phalloides poisoning causes, after a quiet period, acute liver failure through Pol II inhibition.
- Mutations in Pol III subunits cause hypomyelinating leukodystrophies; in Pol I and Pol III subunits, Treacher Collins syndrome.
- Rifampicin is selective because bacterial RNA polymerase differs from the human ones.

## Related conditions

- [Tuberculosis](https://durgical.com/en/conditions/tuberculosis/)

## Related

- [Transcription](https://durgical.com/en/biochemistry/topics/transcription/)
- [RNA processing (cap, poly-A tail and splicing)](https://durgical.com/en/biochemistry/topics/rna-processing/)
- [α-Amanitin](https://durgical.com/en/biochemistry/molecules/amanitin/)
- [Transfer RNA (tRNA)](https://durgical.com/en/biochemistry/topics/transfer-rna/)
- [Central dogma of molecular biology](https://durgical.com/en/biochemistry/topics/central-dogma-of-molecular-biology/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which RNA polymerase makes tRNAs and 5S rRNA?

RNA polymerase III.

## How do the three RNA polymerases rank by sensitivity to α-amanitin?

Pol II is the most sensitive, Pol III intermediate and Pol I resistant.

## What does the 3D model 8WB0 show?

Mammalian Pol II (pig, almost identical to human) transcribing, with a modified guanine nucleotide (W0F) bound next to the catalytic site.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [POLR2A: DNA-directed RNA polymerase II subunit RPB1 (human)](https://www.uniprot.org/uniprotkb/P24928/entry) (UniProt, 2026); [8WB0: De novo transcribing complex 17 (TC17), the early elongation complex with Pol II positioned 17nt downstream of TSS](https://www.rcsb.org/structure/8WB0) (RCSB Protein Data Bank, 2026); [RNA Polymerase I Transcription](https://reactome.org/PathwayBrowser/#/R-HSA-73864) (Reactome, 2026); [RNA Polymerase II Transcription](https://reactome.org/PathwayBrowser/#/R-HSA-73857) (Reactome, 2026); [RNA Polymerase III Transcription](https://reactome.org/PathwayBrowser/#/R-HSA-74158) (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.

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