Initiation of translation

Antisense therapy means the selective, sequence-specific inhibition of gene expression by single-stranded DNA oligonucleotides. By hybridizing to the target mRNA, which results in a subsequent double-helix formation, gene expression is blocked. This process can occur at any point between the conclusion of transcription and initiation of translation or even possibly during translation. 

Kozak M Structural features in eukaryotic mRNAs that modulate the initiation of translation. J Biol Chem 1991 266 1986. 

The mDHFR protein complementation assay has been used to map a signal transduction network that controls the initiation of translation in eukaryotes (Remy and Michnick, 2001). A total of 35 different pairs of full-length proteins were analyzed and 14 interactions were identified using the survival selection of cells grown in the absence of nucleotides. In addition, the use of the fMTX reagent in combination with fluorescence microscopy was used to localize the protein complex within cells (Remy and Michnick, 2001). 

Thomas It is not the only place that it is regulated. Elongation is also regulated, but most of the input is at the level of the initiation of translation. 

Borman, A. M., and Kean, K. M. (1997). Intact eukaryotic initiation factor 4G is required for hepatitis A virus internal initiation of translation. Virology 237, 129-136. 

Olsen, P. H., and Ambros, V. (1999). The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev. Biol. 216, 671—680. 

Rau, M., Ohlmann, T., Morley, S. J., and Pain, V. M. (1996). A reevaluation of the capbinding protein, eIF4E, as a rate-limiting factor for initiation of translation in reticulocyte lysate. J. Biol. Chem. 271, 8983—8990. 

Lomakin, I. B., Hellen, C. U., and Pestova, T. V. (2000). Physical association of eukaryotic initiation factor 4G (eIF4G) with eIF4A strongly enhances binding of eIF4G to the internal ribosomal entry site of encephalomyocarditis virus and is required for internal initiation of translation. Mol. Cell Biol. 20, 6019-6029. 

Pause, A., Methot, N., Svitkin, Y., Merrick, W. C., and Sonenberg, N. (1994). Dominant negative mutants of mammalian translation initiation factor eIF-4A define a critical role for eIF-4F in cap-dependent and cap-independent initiation of translation. EMBO J. 13, 1205-1215. 

Hunt, S. L., Hsuan, J. J., Totty, N., and Jackson, R. J. (1999). Unr, a cellular cytoplasmic RNA-binding protein with five cold-shock domains, is required for internal initiation of translation of human rhinovirus RNA. Genes Dev. 13, 437—448. 

Protein biosynthesis by eukaryotic ribosomes, which are larger and more complex than those of bacteria, is very similar in its basic outline to that of bacteria. The major difference is in the initiation of translation, which involves recognition of the 5 -cap on the mature mRNA, mentioned earlier, by the small ribosomal subunit. 

Garceau NY, Liu Y, Loros JJ, Dunlap JC 1997 Alternative initiation of translation and time-specific phosphorylation yield multiple forms of the essential clock protein FREQUENCY. Cell 89 469-476... 

The translation of the correctly modified mature mRNA by the ribosome is also subject to regulation. The regulatory site of translation is mainly at the initiation of translation. Further regulatory elements include the availability of mRNA for ribosomal protein biosynthesis, as well as the concentration of mRNA. The availabihty of mRNA can be controlled by, for example, sequence-specific protein binding to the mRNA. The concentration of a specific mRNA is determined by a balance between its rate of synthesis (i.e. transcription) and its rate of degradation by RNases. The stabihty of a mRNA against nucleolytic degradation is thus a further factor that can determine the extent of biosynthesis of a protein. 

Capping at the 5 -end of the pre-mRNA occurs immediately after incorporation of about 30 nucleotides in the primary transcript. The 5 cap structure is required for the binding of the mRNA to the 40S subunit of the ribosome during the initiation of translation. Capping is also ascribed a stabilizing function for mRNA. 

Hie regulation of the ferritin concentration is also related to the iron concentration. Hie vulnerable point is not the stability of the mRNA, but rather of the initiation of translation. Hie mRNA for ferritin possesses a hairpin structure in the 5 - non-coding... 

The above mentioned examples illustrate the variety of regulatory mechanisms under the control of eIF-2. Together, they play a central role in the control of initiation of translation in eucaryotes. 

Changes in the code need not be absolute a codon might not always encode the same amino acid. In E. coli we find two examples of amino acids being inserted at positions not specified in the normal code. The first is the occasional use of GUG (Val) as an initiation codon. This occurs only for those genes in which the GUG is properly located relative to particular mRNA sequences that affect the initiation of translation (as discussed in Section 27.2). 

The codon AUG signals initiation of translation. The triplets UAA, UAG, and UGA are signals for termination. 

TABLE 27-8 Protein Factors Required for Initiation of Translation in Bacterial and Eukaryotic Cells... 

Rezniczek, G. A., Abrahamsberg, C., Fuchs, P., Spazierer, D., and Wiche, G. (2003). Plectin 5 -transcript diversity Short alternative sequences determine stability of gene products, initiation of translation and subcellular localization of isoforms. Hum. Mol. Genet. 12, 3181-3194. 

Pelletier, J. and Sonnenberg, N. (1988) Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature 334, 320-325. 

The existence of the extremely short 5 untranslated mRNA of many halobacterial mRNAs raises the question of the location of the signals for the initiation of translation (equivalent to the Shine-Dal-garno sequences). In some cases it is possible to detect a sequence complementary to the 3 end of the 16S rRNA at the 5 untranslated transcripts [as in the cases of sop (Blanck et al., 1989), the genes coding... 

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