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Transcription by RNA polymerase III: more complex than we thought


RNA polymerase (Pol) III is highly specialized for the production of short non-coding RNAs. Once considered to be under relatively simple controls, recent studies using chromatin immunoprecipitation followed by sequencing (ChIP–seq) have revealed unexpected levels of complexity for Pol III regulation, including substantial cell-type selectivity and intriguing overlap with Pol II transcription. Here I describe these novel insights and consider their implications and the questions that remain.

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Figure 1: Basal transcription machinery and promoter structure at RNA polymerase III-transcribed genes.
Figure 2: Schematic comparison of features distinguishing many active and inactive tRNA genes.
Figure 3: How specific histone modifications correlate with expression of RNA polymerase III- and RNA polymerase II-transcribed genes.


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The author gratefully acknowledges funding from Cancer Research UK.

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(5S ribosomal RNA). The smallest of the rRNAs. It is found in the large subunit of ribosomes.


Binds and represses P-TEFb, a factor that stimulates transcript elongation by RNA polymerase II.


Acts as a scaffold within the signal recognition particle (SRP), which inserts nascent polypeptides into membranes.


The RNA component of RNase P, which processes the 5′ end of tRNAs.


Human Y RNA, which has putative roles in DNA replication and quality control of non-coding RNAs.


Mitochondrial RNA processing (MRP) RNA is part of a ribonucleoprotein particle that processes precursor ribosomal RNA and mitochondrial DNA replication primers. MRP RNA (encoded by the RMRP gene) also associates with the catalytic subunit of human telomerase reverse transcriptase (TERT) to form an RNA-dependent RNA polymerase which generates RNAs that are processed by DICER into small interfering RNAs.

SANT domain

A motif of ~50 amino acid residues that is found in transcription cofactors, chromatin-remodelling proteins and BDP1.

U6 snRNA

(U6 small nuclear RNA). A component of splicesomes, which are required for splicing precursor mRNAs.

Vault RNA

Part of a very large ribonucleoprotein particle that is implicated in multidrug resistance and intracellular transport. Although 20% of vault RNA is found in vault particles, ~80% is free in the cytosol, where it is processed by DICER to generate small intefering RNAs that downregulate CYP3A4, a key enzyme in drug metabolism.

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White, R. Transcription by RNA polymerase III: more complex than we thought. Nat Rev Genet 12, 459–463 (2011).

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