Transcription begins when a complex forms between polymerase II (pol II), five transcription factors; TFIIB, TFIID, TFIIE, TFIIF, and TFIIH, and a mediator. TFIIB and TFIID are key transcription factors that are responsible for recognizing the promoter region on the DNA strand.  The TFIID binds with DNA at the TATA box causing the DNA to bend around the C-terminal of TFIIB (2).  This orients DNA to be unwound and allowing for the template strand to enter the active site of pol II.  Part of the pol II forms a clamp that swings closed once the DNA promoter region has bound to the pol II complex.

The other three transcription factors mentioned before all play their own role in the initiation of transcription.  Transcription factor TFIIF interacts with the non-template DNA strand, to prevent it from trying to rebind to the template strand (2).  TFIIE plays a role in coupling pol II and TFIIH.  Finally TFIIH works to open the DNA strand; starting to separate the stands in order for a single template strand to be achieved.  This then begins the second stage of transcription elongation.  The mediator is required to transmit regulatory signals to pol II.

Elongation begins with the unwinding of the DNA stand to form a single stranded template.  Unwinding starts downstream from the binding site about five residues.  The strands begin coming back together at this point and so appear to be frayed.  The strands are kept apart by interactions with the Lys1109 and Asn1110 residues on the RPB1 subunit of pol II (7).  This forms what is called the transcription bubble and allows the single template stand to enter the active site.

In the active site ribonucleotides will be added by matching them to the template strand of DNA.  The active site is composed of two metal ions that are distinct but somewhat overlap.  The first site is termed the A site and is located by the Rpb1 subunit residues Asp481, Asp483, and Asp485 and coordinates with the a-phosphate of the NTP (7). The second site, the E site, is located near residues Asp481, Asp483 on the Rpb1 subunit and Asp836 on the Rpb2 subunit, and coordinates with the b and g phosphates of the NTP.  If the ribonucleotide that enters active site is the correct match then it enters site A and is positioned so that the a-phosphate of the NTP can be attacked by the 3’ OH group of the RNA chain forming a phosphodiester bond.  It is also possible for a mismatched ribonucleotide to enter the active site.  When this happens is binds to the E site and is flipped upside down and therefore does not add to the growing RNA strand. 

Once the bond is formed the DNA-RNA hybrid is moved upstream so that the A and E sites are now open for a new match to be formed.  As the DNA-RNA hybrid keeps moving it comes into contact with three loops that aid in the splitting of these two strands (4).  First is the rudder which causes the RNA and DNA to be split and the RNA to start to move toward the exit site.  The RNA passes by the second loop, the lid, which aids in keeping the RNA separated from the DNA template.  Finally is the zipper which plays a role in maintaining the upstream end of the transcription bubble.

The elongation phase of transcription will continue until the termination sequence on the DNA strand is reached.  Once this sequence is read pol II stops adding ribonucleotides and TFIIS cleaves the RNA strand at the active site (4).  The RNA is then completely separated from the DNA strand and the pol II complex falls apart.  This allows the DNA strand to completely reform and leaves you with a strand of mRNA that is complementary to the DNA template.