14. Summary

20.14 Summary

Of the three eukaryotic RNA polymerases, RNA polymerase I transcribes rDNA and accounts for the majority of activity, RNA polymerase II transcribes structural genes for mRNA and has the greatest diversity of products, and RNA polymerase III transcribes small RNAs. The enzymes have similar structures, with two large subunits and many smaller subunits; there are some common subunits among the enzymes.

None of the three RNA polymerases recognize their promoters directly. A unifying principle is that transcription factors have primary responsibility for recognizing the characteristic sequence elements of any particular promoter, and they serve in turn to bind the RNA polymerase and to position it correctly at the startpoint. At each type of promoter, the initiation complex is assembled by a series of reactions in which individual factors join (or leave) the complex. The factor TBP is required for initiation by all three RNA polymerases. In each case it provides one subunit of a transcription factor that binds in the vicinity of the startpoint.

The TATA box (if there is one) near the startpoint, and the initiator region immediately at the startpoint, are responsible for selection of the exact startpoint at promoters for RNA polymerase II. TBP binds directly to the TATA box when there is one; in TATA-less promoters it is located near the startpoint by other means. After binding of TFIID, the general transcription factors for RNA polymerase II assemble the basal transcription apparatus at the promoter, and are mostly released when RNA polymerase begins elongation.

RNA polymerase is found as part of much larger complexes that contain factors that interact with activators and repressors. A common point of contact for RNA polmerase with these proteins is its CTD, which is phosphorylated during the initiation reaction. TFIID and SRB proteins both may interact with the CTD. It may also provide a point of contact for proteins that modify the RNA transcript, including the 5′capping enzyme.

Promoters for RNA polymerase II contain a variety of short cis-acting elements, each of which is recognized by a trans-acting factor. The cis-acting elements are located upstream of the TATA box and may be present in either orientation and at a variety of distances with regard to the startpoint. The upstream elements are recognized by transcription factors that interact with the basal transcription complex to determine the efficiency with which the promoter is used. Some upstream factors interact directly with components of the basal apparatus; others interact via coactivators. The targets in the basal apparatus are the TAFs of TFIID, or TFIIB or TFIIA. The interaction stimulates assembly of the basal apparatus.

Promoters may be stimulated by enhancers, sequences that can act at great distances and in either orientation on either side of a gene. Enhancers also consist of sets of elements, although they are more compactly organized. Some elements are found in both promoters and enhancers. Enhancers probably function by assembling a protein complex that interacts with the proteins bound at the promoter, requiring that DNA between is "looped out."