Eukaryotes chain initiation

Goss, D. J., Parkhurst, L. J., Mehta, H. B., Woodley, C. L., and Wahba, A.J. (1984). Studies on the role of eukaryotic nucleotide exchange factor in polypeptide chain initiation. 

Abbreviations aa-tRNA Amino-acyl tRNA eLF Eukaryotic translation initiation factor IF Prokaryotic translation initiation factor eEF Eukaryotic translation elongation factor EF Prokaryotic translation elongation factor eRF Eukaryotic translation termination factor (release factor) RF Prokaryotic translation release factor RRF Ribosome recycling factor Rps Protein of the prokaryotic small ribosomal subunit Rpl Protein of the eukaryotic large ribosomal subunit S Protein of the prokaryotic small ribosomal subunit L Protein of the prokaryotic large ribosomal subunit PTC Peptidyl transferase center RNC Ribosome-nascent chain-mRNA complex ram Ribosomal ambiguity mutation RAC Ribosome-associated complex NMD Nonsense-mediated mRNA decay... 

For most polypeptide chains initiation begins with one of the three initiation codons, most commonly the methionine codon AUG. When properly placed in an mRNA chain, GUG may also serve as a bacterial initiation codon. In such cases, it codes for methionine rather than for valine. Occasionally UUG, AUU, ACG, and perhaps other codons can initiate translation 288/289 This is less frequent in eukaryotes than in bacteria. The sequence of bases preceding the initiation codon must also be important for recognition of the "start" signal. 

Be able to describe the mechanism for peptide chain initiation, elongation, and termination in prokaryotes and eukaryotes on the ribosome. 

High concentrations of hemin inhibit the transport of ALA synthase into the mitochondria, where one of the substrates, succinyl-CoA, is formed. Thus, heme synthesis is inhibited until enough globin is made to react with any heme already formed. Low concentrations, or the absence, of hemin is the signal that globin is not needed this protein (and, therefore, globin) synthesis is inhibited. In the absence of hemin, a protein kinase is activated this phosphorylates an initiation factor of (eukaryotic) protein synthesis, eIF-2, which then inhibits polypeptide chain initiation (Chap. 17) and hence inhibits globin synthesis. 

The discovery that dolichol phosphates and pyrophosphates (diphosphates) are carriers for oligosaccharides in eukaryotic cells initiated the modem era of glycoprotein biochemistry. These lipid-linked oligosaccharides are precursors for the carbohydrate side chains of the asparagine-linked glycoproteins. Because of this common precursor, all of the side chains of these glycoproteins share the same carbohydrate core, shown within the dashed box in Figure 16-la. 

Kimball SR, Antonetti DA, Brawley RM, Jefferson LS. 1991. Mechanism of inhibition of peptide chain initiation by amino acid deprivation in perfused rat liver. Regulation involving inhibition of eukaryotic initiation factor 2a phosphatase activity. J Biol Chem 266 1969-1976. 

The details of the chain of events in translation differ somewhat in prokaryotes and eukaryotes. Like DNA and RNA synthesis, this process has been more thoroughly studied in prokaryotes. We shall use Escherichia coli as our principal example, because aU aspects of protein synthesis have been most extensively studied in this bacterium. As was the case with replication and transcription, translation can be divided into stages—chain initiation, chain elongation, and chain termination. 

The general mechanisms by which proteins are synthesized appear to be similar in both prokaryotes and eukaryotes. There are some minor differences, particularly in chain initiation and termination and in designation and chemical characteristics of the various soluble factors. 

Siekierka, J., Mauser, L., and Ochoa, S., 1982, Mechanism of polypeptide chain initiation in eukaryotes and its control by phosphorylation of the a subunit of initiation factor 2, Proc. Natl. Acad. Sci. USA 79 2537. 

Seal, S. N., Schmidt, A., and Marcus, A., 1983, Eukaryotic initiation factor 4A is the component that interacts with ATP in protein chain initiation, Proc. Natl. Acad. Sci. USA 80 6562. 

B. Datta, M.K. Ray, D. Chakrabarti, D.E. Wylie and N.K. Gupta, J. Biol Chem., 1989, 264, 20620-20624, Glycosylation of eukaryotic peptide chain initiation factor 2 (eIF-2)-associated 67-kDa polypeptide (p ) and its possible role in the inhibition of elF-2 kinase-catalyzed phosphorylation of the eIF-2 a-subunit. 

DNA-directed RNA polymerase [EC 2.1.1.6] catalyzes the DNA-template-directed extension of the 3 -end of an RNA strand by one nucleotide at a time thus, n nucleoside triphosphate generate RNA and n pyrophosphate. The enzyme can initiate a chain de novo. Three forms of the enzyme have been distinguished in eukaryotes on the basis of sensitivity of a-amanitin and the type of RNA synthesized. See also Replicase... 

The pathway of protein synthesis translates the three-letter alphabet of nucleotide sequences on mRNA into the twenty-letter alphabet of amino acids that constitute proteins. The mRNA is translated from its 5 -end to its 3 -end, producing a protein synthesized from its amino-terminal end to its carboxyl-terminal end. Prokaryotic mRNAs often have several coding regions, that is, they are polycistronic (see p. 420). Each coding region has its own initiation codon and produces a separate species of polypeptide. In contrast, each eukaryotic mRNA codes for only one polypeptide chain, that is, it is monocistronic. The process of translation is divided into three separate steps initiation, elongation, and termination. The polypeptide chains produced may be modified by posttranslational modification. Eukaryotic protein synthesis resembles that of prokaryotes in most details. [Note Individual differences are mentioned in the text.]... 

The copying of genetic information from DNA into messenger RNA is the initial step in the chain of reactions leading to synthesis of the multitude of proteins and specialized RNA molecules needed by cells. The requirement for these macromolecules varies with conditions, and in eukaryotic cells, with the stage of differentiation. Therefore, it is not surprising that transcription is highly controlled. 

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