MRNA synthesis and

Figure 12.17 Sites at which insulin stimulates protein synthesis in a muscle. The sites are indicated by 0. Insulin has its anabolic effect on protein synthesis in muscle by affecb ng six processes or reactions (i) it inhibits protein degradab on in the muscle (ii) it sb mulates amino acid transport from the blood into the muscle (iii) it stimulates the inib ab on-reacb on of the pathway for protein synthesis, i.e. formab on of the complex (tRNA-amino acid-mRNA-ribosomal RNA) (iv) it increases the rate of mRNA synthesis, and therefore the number of mRNA molecules (v) it stimulates ribosomal RNA synthesis (vi) it sb mulates elongabon of the pepbde (see Chapter 20).

Induction involves increased synthesis of enzyme protein, which may be detected as an increase in total enzyme level as with phenobarbital induction or increase in a particular isoenzyme. Protein synthesis is increased, and this usually seems to be necessary as inhibition of protein synthesis results in inhibition of induction. The increased protein synthesis may involve increased mRNA synthesis and inhibitors of this, such as actinomycin D, block induction. For a simple diagram explaining the relationship of protein synthesis to DNA see Figure 6.38. 

Okamoto, P.M., Fu, Y.-H. Marzluf, G.A. (1991). Nit-3, the structural gene of nitrate reductase in Neurospora crassa nucleotide sequence and regulation of mRNA synthesis and turnover. Molecular and General Genetics 227, 213-23. 

Induction of Calbindin-D In response to calcitriol administration, there is an increase in mRNA synthesis and then in the synthesis of calbindin-D in intestinal mucosal cells, which is correlated with the later and more sustained increase in calcium absorption. In vitamin D-deficient animals, there is no detectable calbindin in the intestinal mucosa, whereas in animals adequately provided with vitamin D, it may account for 1 % to 3% of soluble protein in the cytosol of the colunmar epithelial ceils. Although the rapid response to calcitriol is an increase in the permeability of the brush border membrane to calcium, the induction of calbindin permits intracellular accumulation and transport of calcium. The rapid increase in net calcium transport in tissue from vitamin D-replete animals is presumably dependent on the calbindin that is already present in deficient animals, there can be no increase in calcium transport until sufficient calbindin has accumulated to permit intracellular accumulation, despite the increased permeability of the brush border. 

The increase in ATCase activity in response to increased ATP concentration has tvv o potential physiological explanations. First, high ATP concentration signals a high concentration of purine nucleotides in the cell the increase in ATCase activity will tend to balance the purine and pyrimidine pools. Second, a high concentration of ATP indicates that there is significant energy stored in the cell to promote mRNA synthesis and DNA replication. 

The drug kinetics and receptor dynamics were modeled as before (Section 19.2.1). As depicted in Figure 19.5A, a mechanistic model was proposed to describe the simultaneous actions of CS on PEPCK mRNA synthesis and degradation, induction of cAMP by CS, and translational stimulation by cAMP ... 

There are two steps in protein synthesis where polarity of information is important. The first is the relationship between the 50 to 30 directionality of mRNA, and the NH3+ to COO- terminal direction of protein synthesis. The utilization of tRNA as the adaptor is the second step where polarity of information is crucial. The tRNA has a bipolar function, it needs to correctly link each amino acid to the corresponding position encoded by the mRNA. Figure 26.1 shows an overview of how mRNA synthesis and protein translation share the same polarity. Moreover, similar to transcription, translation can also be broken down into three discrete components initiation, elongation, and termination. 

A number of other cytokines have been shown to regulate mRNA ° synthesis, and a summary of the effects reported for cultured cells is presented in Table 2. Cooperative regulation of NGF synthesis and secretion by cytokines has been observed in cultured astrocytes and fibroblasts (Yoshida and Gage, 1992). 

In contrast to prokaryotes, all eukaryotic cells contain three forms of RNA Pol which perform specialized tasks RNA Pol I (or RNA Pol A) for rRNA synthesis, RNA Pol II (or RNA Pol B) for mRNA synthesis, and RNA Pol III (or RNA Pol C) for synthesis of tRNA, 5S RNA, and small nuclear RNAs. Despite similarities in size (500-600 kDa) and multimeric structure (9—14 polypeptides), the three polymerases have characteristic differences at the subunit level and in the set of associated transcription factors (11). The RNA Pol II transcription system, which is the main subject of this section, is the best charaaerized of the three polymerase transcription systems. 

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