Transcription chain initiation

DNA stores genetic information in a stable form that can be readily replicated. However, the expression of this genetic information requires its flow from DNA to RNA to protein, as was introduced in Chapter 5. The present chapter deals with how RNA is synthesized and spliced. We begin with transcription in Escherichia coli and focus on three questions What are the properties of promoters (the DNA sites at which RNA transcription is initiated), and how do the promoters function How do RNA polymerase, the DNA template, and the nascent RNA chain interact with one another How is transcription terminated ... 

The drug rifampin binds to bacterial RNA polymerases and is a useful experimental inhibitor of initiation of transcription. It binds to the P subunit of RNA polymerase, blocking the transition from the chain initiation phase to the elongation phase it is an inhibitor of chain initiation but not of elongation. Actinomycin D also inhibits initiation but does so by binding to DNA. These drugs have limited clinical use because of their toxicity. 

The process of transcription (and translation as well, as we will see in Chapter 12) is usually broken down into phases for easier studying. The first phase of transcription is called chain initiation, and it is the part of transcription that has been studied the most. It is also the part that is the most controlled. 

Chain initiation requires formation of the open complex. Recent studies show that a portion of the P and the a-subunits initiate strand separation, melting about 14 base pairs surrounding the transcription start site. A purine ribonucleoside triphosphate is the first base in RNA, and it binds to its complementary DNA base at position +1. Of the purines, A tends to occur more often than G. This first residue retains its 5 -triphosphate group (indicated by ppp in Figure 11.3). 

The details of the chain of events in translation differ somewhat in prokaryotes and eukaryotes. Like DNA and RNA synthesis, this process has been more thoroughly studied in prokaryotes. We shall use Escherichia coli as our principal example, because aU aspects of protein synthesis have been most extensively studied in this bacterium. As was the case with replication and transcription, translation can be divided into stages—chain initiation, chain elongation, and chain termination. 

Fig. 11.4. Model of signal transduction via the IL-2 receptor. Binding of IL-2 to the IL-2 receptor initiates activation of the Janus kinases Jakl and Jak3. These phosphorylate tyrosine residues in the P-chain of the IL-2 receptor and in the transcription factor StatS. SH2 domains or PTB domains of adaptor proteins can bind to the Tyr phosphate residues of the P-chain and, as shown in the figure for the Shc/Grb2/Sos complex, can transmit a signal in the direction of the Ras pathway. The phosphorylated transcription factor StatS is translocated into the nucleus and activates the transcription of corresponding gene sections. Another signaling pathway starting from the activated IL-2 receptor involves the Lck and Syk tyrosine kinases (see Chapter 8). The pathway leads to induction of genes for transcription factors such as c-Myc and c-Fos.

Regulation at the transcription level has also been described for the inhibitor pl5 4b, The cytokine TGPp is involved in this regulation (see Chapter 12). Binding of TGPP to its receptor initiates a signal chain that culminates in activation of transcription of the gene for pl5 b and may lead to a halt in the cell cycle. 

The copying of genetic information from DNA into messenger RNA is the initial step in the chain of reactions leading to synthesis of the multitude of proteins and specialized RNA molecules needed by cells. The requirement for these macromolecules varies with conditions, and in eukaryotic cells, with the stage of differentiation. Therefore, it is not surprising that transcription is highly controlled. 

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