Control of translation

Introduction to Signaling Pathways and the Control of Translation Factors... 

The classic example of a reaction that demands control of translational entropy is surely the Diels-Alder cycloaddition. It is accelerated by high pressure and by solutions 8 m in LiCl (Blokzijl and Engberts, 1994 Ciobanu and Matsumoto, 1997 Dell, 1997) and proceeds through an entropi-cally disfavoured, highly ordered transition state, showing large activation entropies in the range of -30 to -40 cal mol-1 K 1 (Sauer, 1966). 

Fig. 1.52. Model for the control of translation by tubulin. The amount of tubuhn in animal cells is determined partially by the stabrhty of P-tubuhn mRNA, whereby tubuhn itself acts as the regulating signal. Starting from the 5 cap, various stages of the translation of P-tubuhn mRNA, represented as a chain of small circles, is illustrated in the figure. As soon as the N-terminus of the growing P-chain emerges from the ribosome, the a- and P- subunits of tubulin bind to the terminal MREI sequence, upon which an endonuclease becomes activated by a presently unknown mechanism. The degradation of the P-tubulin mRNA then proceeds.

Fig. 1.54 Principle of negative control of translation initiation by protein binding to mRNA. Proteins can negatively effect translation by binding to the sequences in the 5 non-translated region of their own or other mRNAs. The participating proteins are sequence-specific RNA binding proteins and recognize RNA sequences in hairpin structures or other secondary structures of RNA. The protein binding interferes with the scanning of ribosomes and prevents the translation of mRNA.

Proud, C.G and Denton, R.M. Molecular mechanism for the control of translation by insulin ... 

Gray, N.K. Wickens, M. (1998) Control of translation initiation in animals. Annu. Rev. Cell Dev. Biol. 14, 399-458. 

Proud, C. G., Guanine nucleotides, protein phosphorylation and control of translation. Trends Biochem. Sci. 11 73-77,... 

Kocarek, T. A., R. C. Zanger, and R. F. Novak. Post-transcriptional regulation of rat CYP2E1 expression Role of CYP2E1 mRNA untranslated regions in control of translational efficiency and message stability. Arch. Biochem. Biophys. 376 180-190, 2000. 

Optimization of mRNA Sequence and Structure for Effective Control of Translation... 

The translation of mRNA to protein concludes the gene expression cascade and links the proteome to the genome. Consequently, control of translation can be a direct and effective means to modulate the proteome [21, 30, 31]. In addition to transcript interactions with protein regulators, translation is also modulated by structural features or regulatory sequences appearing within the mRNA molecules. The 7-methylguanylate triphosphate nucleotidyl caps at the 5 end, poly-A tails, uORFs, and IRESs are examples of structures that affect the rate and efficiency of translation in eukaryotes [21]. 

The list of examples detailed above is by no means exhaustive. Several additional examples of the structure-based control of translation, such as repressor protein binding sequences on the mRNA transcripts and ribozymes [39], are among others that could be listed. The intentions of this chapter are not to enumerate examples of how structural characteristics of mRNA influence its translation. What should be evident from the preceding discussion is that mRNA structure is a critical determinant of translation, and synthetic DNA technology offers the possibility to alter and probe the effects of mRNA sequence on its structure and the resulting translation efficiency. Further developments in this area will be immensely valuable to metabolic engineering as it will enable practitioners to fine-tune the fluxes of desired metabolic pathways through modulation of protein levels. 

Dufner A, Thomas G. Ribosomal S6 kinase signaling and the control of translation. Exp. Cell. Res. 1999 253 100-109. 

C. G. Proud and R. M. Denton Molecular Mechanisms for the control of translation of insulin. Biochemical Journal 328,329 (1997). 

The Diels-Alder reaction is one of the most useful carbon-carbon bond-forming reactions in organic chemistry and can lead to the rapid assimilation of complex molecules containing a high degree of asymmetry. It is a bimolecular process and is a classic example of a reaction that demands control of translational entropy. It is accelerated by both high pressure and ionic solutions (8 M LiCl) and... 

See also Control of Translation, Translation Overview (from Chapter 27), Initiation of Translation (from Chapter 27), Elongation of Translation (from Chapter 27), Termination of Translation (from Chapter 27), Antibiotic Inhibition of Translation (from Chapter 27)... 

Antisense is by no means an artificial concept. Apart from basic coding/non-coding strand interactions, a series of cases has been found in nature, in which gene regulation is effected by antisense-type nucleic acid/nucleic acid interactions. Frequently, control of translation and accelerated depletion of target mRNA is effected by antisense ODNs in eucaryotic organisms like yeast, insects or mammals. In Table 2 a series of reported natural sense/antisense interaction is listed. In case given, sequences involved in such interactions are also potential elements of therapeutic antisense action. 

An example of the role of mRNA degradation in control of translation is provided by the transferrin receptor mRNA (Eig. 16.24) The transferrin receptor is a... 

Although the nature of the bacterial cell makes possible specific control over transcription in ways that cannot be achieved in eukaryotic systems, control of gene expression at the level of translation is also important in bacteria. Control of translation is achieved primarily by the prevention of ribosomal binding. 

Sonenberg, N. (1988). Cap-binding proteins of eukaryotic messenger RNA Functions in initiation and control of translation. Prog. Nucleic Acid Res. Mol. Biol. 35,173-207. 

Control of translation at the level of initiation has also been reported in cultured mammalian cells during incubation at 42°C (McCormick and Penman, 1969) and during mitosis (Fan and Penman, 1969). The limiting factor for initiation at 42° appears to be an unidentified, labile RNA species, the synthesis of which is increased when translation is decreased. During mitosis the overall rate of protein synthesis is reduced... 

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