During the course of evolution, as organisms transitioned from an RNA genome into a DNA genome, two immediate requirements needed to be fulfilled. First, RNA-template dependent DNA synthesis, which forms the principal form of replication in retroviruses and is still observed in retrotransposable elements in humans. Second, DNA-template dependent RNA synthesis, which is carried out by RNA polymerase (RNAP) in both bacteria and eukaryotes.
Transcription can be divided into three main stages, each involving distinct DNA sequences to guide the polymerase. These are:
Bacterial RNAP carries out all three steps in conjunction with other accessory proteins. While some RNA polymerases such as the viral T7 and N4 polymerases are composed of a single polypeptide chain, all organisms with cellular genomes have multisubunit polymerases that vary in size and complexity, depending on the structure of the genome. The multisubunit structure of the bacterial RNAP helps the enzyme to maintain catalytic function, facilitate assembly, interact with DNA and RNA, and self-regulate its activity. While it is a catalytically efficient enzyme, it does not recognize DNA sequences specifically. To help the RNAP recognize DNA sequences with high affinity, specialized proteins called transcription factors bind to particular regions of DNA to initiate and terminate transcription. Of all the specialized proteins that assist the RNAP, only one is conserved in all three domains of life- bacteria, archaea and eukaryotes. This transcription factor is called NusG in bacteria, Spt5 in archaea and SPT5 in eukaryotes. NusG binds to RNA polymerase during initiation once the σ factor has dissociated. It regulates transcription processivity by controlling polymerase pausing. The universal conservation of NusG indicates that regulation of polymerase activity during elongation predated regulation of transcription initiation.
