InterPro domain: IPR001529

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.

In archaebacteria, there is generally a single form of RNA polymerase which also consist of an oligomeric assemblage of 10 to 13 polypeptides.It has recently been shown [ 3 , 4 ] that small subunits of about 15kDa, found in polymerase types I and II, are highly conserved. These proteins contain a probable zinc finger in their N-terminal region and a C-terminal zinc ribbon domain (see IPR001222 ).

Proteins containing this domain also include transcription factor S (TFS), a protein related in size and sequence to DNA-directed RNA polymerase subunit M, and in sequence and function to the much larger eukaryotic transcription factor IIS (TFIIS). Although originally suggested to be a subunit of the archaeal RNA polymerase (known as archaeal DNA-directed RNA polymerase subunit M), it elutes separately from active polymerase in gel filtration experiments and acts, like TFIIs, as an induction factor for RNA cleavage by RNA polymerase [ 5 , 6 ].

1. Structure and function of bacterial sigma factors. Annu. Rev. Biochem. 57, 839-72
2. Crystal structure of Thermus aquaticus core RNA polymerase at 3.3 A resolution. Cell 98, 811-24
3. Structure of the gene encoding the 14.5 kDa subunit of human RNA polymerase II. Nucleic Acids Res. 21, 5345-50
4. Gene RRN4 in Saccharomyces cerevisiae encodes the A12.2 subunit of RNA polymerase I and is essential only at high temperatures. Mol. Cell. Biol. 13, 114-22
5. Transcription factor S, a cleavage induction factor of the archaeal RNA polymerase. J. Biol. Chem. 275, 12393-9
6. Transcriptional fidelity and proofreading in Archaea and implications for the mechanism of TFS-induced RNA cleavage. Mol. Microbiol. 52, 1133-43