Regulation of mRNA Synthesis

Regulation of mRNA synthesis Regulation of gene expression... 

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. 

The regulation of receptor synthesis is a second component of receptor downregulation. It involves processes that reduce gene transcription, mRNA stability, and receptor half-life time. It should be noted that mechanisms in addition to the regulation of the receptor number may account for tolerance development. Second messenger levels and enzyme activities that participate in the signaling of a given receptor are... 

Finally, this section has focused almost entirely on axonal transport, but dendritic transport also occurs [25]. Since dendrites usually include postsynaptic regions while most axons terminate in presynaptic elements, the dendritic and axonal transport each receive a number of unique proteins. An added level of complexity for intraneuronal transport phenomena is the intriguing observation that mRNA is routed into dendrites where it is implicated in local protein synthesis at postsynaptic sites, but ribosomal components and mRNA are largely excluded from axonal domains [26]. Regulation of protein synthesis in dendritic compartments is an important mechanism is synaptic plasticity [27,28]. The importance of dendritic mRNA transport and local protein synthesis is underscored by the demonstration that the mutation associated with Fragile X syndrome affects a protein important for transport and localization of mRNA in dendrites [27, 29], Similar processes of mRNA transport have been described in glial cells [30]. 

The intercalating drugs and nucleic acid synthesis inhibitors discussed in the preceding sections interfere indirectly with every phase of nucleic acid action because the DNA is rendered nonfunctional. Other drugs, discussed below, affect the regulation of protein synthesis even when the genome, the DNA structure, is intact. Such activity can be the result of interference either with transcription of messenger RNA or with translation of the mRNA to protein. 

For years, it was assumed that the rate of RNA synthesis was the rate-limiting step that controls indirectly the amount of protein synthesized. However, this simplistic view has been replaced by results clearly showing that mRNA and protein levels do not always correlate fully, and that extensive regulation of mRNA transcript processing and availability for translation occurs. 

The synthesis of LDL receptor is itself subject to feedback regulation. The results of studies of cultured fibroblasts show that, when cholesterol is abundant inside the cell, new LDL receptors are not synthesized, and so the uptake of additional cholesterol from plasma LDL is blocked. The gene for the LDL receptor, like that for the reductase, is regulated by SREBP, which binds to a sterol regulatory element that controls the rate of mRNA synthesis. 

Ferritin and transferrin receptor expression levels are reciprocally related in their responses to changes in iron levels. When iron is scarce, the amount of transferrin receptor increases and little or no new ferritin is synthesized. Interestingly, the extent of mRNA synthesis for these proteins does not change correspondingly. Instead, regulation takes place at the level of translation. 

The basal transcription complex described in Chapter 29 initiates transcription at a low frequency. Recall that several general transcription factors (the preinitiation complex) join with KNA polymerase II to form the transcription complex. Additional transcription factors must bind to other sites for a gene to achieve a high rate of mRNA synthesis. In contrast with the regulators of prokaryotic transcription, few eukaryotic transcription factors have any effect on transcription on their own. Instead, each factor recruits other proteins to build up large complexes that interact with the... 

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