RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.

All three eukaryotic RNAPs require specific transcription factors, of which the TATA-binding protein is common to all. These proteins remain attached to the RNAP to guide the direction of RNA synthesis on the template DNA strand.

Once the RNAP has begun elongation, the transcription factors are released from the DNA, so that they can initiate another round of transcription with a new RNA polymerase molecule. The RNAP now binds strongly to the DNA template and continues to synthesize the RNA transcript for lengthy sequences long distances, without dissociating from DNA.

Unlike the termination signals encoded by bacterial genes, the protein-encoding genes transcribed by RNA Polymerase II lack specific sequences that direct the enzyme to terminate at precise locations. The most common termination pathway, known as the Poly(A) dependent termination, combines polyadenylation of the mRNA transcript with RNAP termination. Here, while the RNA Polymerase II continues to transcribe RNA, sometimes upto thousands of basepairs past the end of the gene sequence, the transcript is cleaved at an internal site. Thus the upstream part of the transcript is released and a polyadenine tail can be added to the 3’ end of the cleaved transcript. The downstream cleavage product is digested by a 5′-exonuclease while it is still being transcribed by the RNA Polymerase II. When the 5′-exonulease digests all of the remainder transcript, it helps the RNAP to dissociate from its DNA template strand, thus completing the transcription.