Ribosomes compartmentalization

The mRNA of eucaryotes does not possess specific initiation sequences. Rather, the AUG start codon is identified by scanning the eucaryotic mRNA the 40S subunit of the ribosome threads the 5 non-translated end of the mRNA and uses the first AUG codon encountered to initiate translation. Whether an AUG codon is used as an initiator depends, additionally, upon the sequence context. If the sequence environment is unfavorable for initiation, then the scanning is continued and initiation occurs at one of the next AUGs. With the help of this leaky scanning strategy, it is possible to produce proteins with different N-termini from the same mRNA. Since there are often signal sequences found at the N-terminus, this mechanism may lead to alternative compartmentalization of a protein. 

Figure 3.3 Depiction of a eukaryotic (animal) cell. All eukaryotic cells have evolved with significant compartmentalization resulting in spacio-temporal separation of transcription and translation. DNA is transcribed to mRNA in the nucleus before being shuttled out of the nucleus for translation in the cytosol where ribosomes are located (Reproduced from Voet Voet, 1995 [Wiley] Fig. 1-5).

The main feature of normal animal cell is its compartmentalization [7]. The DNA of the animal cell is restricted to the nucleus at all cell cycle stages except during metaphase when no nucleus exists. The synthesis of RNA occurs in the nucleus and most of it remains there, but messenger RNA and transfer RNA migrate to the cytoplasm. Ribosomal RNA is synthesized in the nucleolus the two ribosomal subunits are partly assembled in the nucleolus and nucleus then migrate to the cytoplasm. All protein synthesis proceed in the cytoplasm. The mitochondria, which is located only in the cytoplasm, contains DNA-s, RNA- and protein-synthesizing systems of their own [7]. 

Specific codons in mRNA signal the initiation and termination of synthesis of each protein. And there exist within the ribosome a number of factors which permit the stepwise synthesis of the polypeptide. In addition, soluble factors are required for initiation, elongation, translocation, and termination. In prokaryotes, translation is closely linked temporally to transcription, since both processes take place in the same milieu in eukaryotes, the nucleus compartmentalizes these two processes, permitting further controls and delaying the coupling of translation to transcription. 

Both prokaryotic and eukaryotic RNA polymerases are composed of several subunits. Although only one form of RNA polymerase predominates in bacteria and blue-green algae, in eukaroytes there are multiple forms of RNA polymerase which have different nuclear and organelle compartmentalization, function, and subunit composition. Polymerase I (or A) is located in the nucleolus and transcribes 18 S and 28 S ribosomal RNA genes. By contrast, polymerase II (or B) and III (or... 

These studies indicate that the major outer membrane proteins (and possibly some cytoplasmic membrane proteins) are produced in a somewhat different manner than the cytoplasmic proteins. Furthermore, it appears that individual outer membrane proteins have their own specific biosynthetic systems. It has been suggested that such specific systems for the outer membrane protein biosynthesis may be achieved by one mechanism or a combination of the following mechanisms (a) differentiation of ribosomes, (b) compartmentalization of ribosomes, and (c) differentiation of factors required for protein synthesis. ... 

Differential inhibitory effects of antibiotics on the synthesis of membrane and cytoplasmic proteins may be due to differences in the ribosomes themselves. Differences in the ribosomes of E, coli may result from the protein components or the RNA components. In fact, some ribo-somal proteins have been shown to be present in only a fraction of ribosomes, resulting in a heterogeneity of ribosomes. The fact that there are several nonlinked ribosomal RNA genes in an E. coli genome may reflect the differentiation of ribosomes. This differentiation of ribosomes may be the direct cause of the different sensitivities of ribosomes to antibiotics. Alternatively, the different sensitivities of ribosomes to antibiotics could be caused indirectly as a result of compartmentalization of ribosomes inside the cell. Existence of a subpopulation of ribosomes with different sensitivities has been suggested for MS2 phage protein synthesis and for a and 0 chains of hemoglobin in rabbit erythrocytes. ... 

Ribosomes may be present in different compartments inside the cells, depending on their functions. This could account for differences in sensitivity of ribosomes to antibiotics. Such compartmentalization may be possible even if all the ribosomes inside the cells are identical. In bacteria, some ribosomes are known to be attached to membranes or a DNA-membrane complex. Recently, Cancedda and Schlesinger reported... 

These questions must be examined with regard to local circumstances of biosynthesis. In cells, proteins are synthesized either by free polysomes or by rough endoplasmic reticulum (RER) membrane-bound polysomes. For nascent polypeptide chains, these two different situations have to be considered since, in the second case, compartmentalization leads to a vectorial transport and discharge through the membrane. Bound and free polysomes seem to derive from a common precursor pool of ribosomes. Several lines of evidence indicate that membrane-bound ribosomal subunits readily exchange in vivo and no major differences in the rRNA sequences and organization of free and bound ribosomes have been found (Fern and Garlik, 1976 see Shore and Tata, 1977). 

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