InterPro domain: IPR035698

DNA-directed RNA polymerases 2.7.7.6 (also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimericenzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [ 1 ]. The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length [ 2 ]. The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

• RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.
• RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.
• RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.

RPC1 (C160) subunit forms part of the active site region of RNA polymerase III (RNAP III). The C-terminal domain of Rpb1, the largest subunit of RNAP II, makes up part of the foot and jaw structures of RNAP II. The similarity between this domain and the C-terminal domain of Rpb1, its counterpart in RNAP II, suggests a similar functional and structural role [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ].

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2. Crystal structure of Thermus aquaticus core RNA polymerase at 3.3 A resolution. Cell 98, 811-24
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10. Mutations in the alpha-amanitin conserved domain of the largest subunit of yeast RNA polymerase III affect pausing, RNA cleavage and transcriptional transitions. EMBO J. 15, 618-29