Gene Translation control

In 1976, Hamish Munro proposed a model for the translational control of ferritin synthesis (Zahringer et al., 1976), which not only represents a crucial and remarkably far-sighted contribution to our understanding of cellular iron metabolism, but also in the more general context of the posttranscriptional control of gene expression. 

Pavitt, G. D. (2005). eIF2B, a mediator of general and gene-specific translational control. Biochem. Soc. Trans. 33, 1487—1492. 

Donahue, T. (2000). Genetic approaches to translation initiation in Saccharomyces cerevisiae. In Translational Control of Gene Expression (N. Sonenberg, J. W. B. Hershey, and M. B. Mathews, eds.), pp. 487—502. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. 

DeFatta, R., Li, Y., and De Benedetti, A. (2002). Selective killing of cancer cells based on translational control of a suicide gene. Cancer Gene Ther. 9, 573-578. 

Translation of the information encoded in DNA, expressed as a particular nucleotide sequence, into a protein, expressed as an amino acid sequence, depends on the genetic code. In this code, sequences of three nucleotides (termed a codon) represent one of the 20 amino acids that compose the protein molecule. Because there are 64 codons which can be constructed for the four different bases, and only 20 different amino acids that are coded for, several amino acids may be coded for by more than one codon. There are also three codons, called stop codons, that terminate the transfer of information. Furthermore, although all cells contain the same complement of genes, certain cells (for example, the neurons) have specialized genes that encode specific proteins for the synthesis of specific transmitters. The expression of such genes is under the control of regulatory proteins called transcription factors which control the transcription of mRNAs from the genes they control. 

Another way in which gene expression is regulated is by translational control, where the rate of protein synthesis is controlled at the point of transcription of mRNA into polypeptides (Appendix 5.6). Generally, the majority of the control mechanisms in bacteria is at the transcriptional level. Translational control is less well understood and appears to be a secondary mechanism in bacteria, but it is thought to be very important in eukaryotic organisms. 

McCarthy, E.G. and Gualerzi, C. (1990) Translational control of prokaryotic gene expression. Trends Genet. 6, 78-85. 

Eukaryotes potentially have many more opportunities for control of gene expression than do bacteria. For example, the cell could take advantage of control at the level of the processing of primary transcripts. It is known that RNA is not transported across the nuclear membrane until all introns are excised. A more subtle form of control could involve alternative modes of splicing a particular transcript. There are now examples known where this occurs to yield different mRNA molecules. Perhaps one of the best-known examples of yet another level of control in eukaryotes is that of translational control of globin synthesis. 

RNAs produced in vitro are useful in the development of in vitro splicing systems where the RNA produced is a primary transcript. In addition, the RNA can be used as a template for in vitro translation, and in mapping exons tuid introns in genomic DNA. Genes under control of bacteriophage promoters can also be expressed in bacterial cells to facilitate expression and/or purification of the proteins they encode. 

Thanbichler M, Bock A. The function of SECIS RNA in translational control of gene expression in Escherichia coli. EMBO J. 73. 2002 21 6925-6934. 

In the liver, cholesterol synthesis is regulated by changes in the amount and activity of 3-hydroxy-3-methylglutaryl CoA reductase. Transcription of the gene, translation of the mRNA, and degradation of the enzyme are stringently controlled. In addition, the activity of the reductase is regulated by phosphorylation. 

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