residue, and therefore the first codon in the coding sequence should be that of methionine. In most cases AUG, and less frequently GUG or UUG (in Prokaryotes), play the role of the initiation codon (see Chapter 15). The codon AUG codes for methionine both when it is the first codon of the mRNA coding sequence and when it occurs in internal positions. The codon GUG, however, codes for valine in internal positions and for the initiator methionine only if it occupies the first position in the coding sequence. The same is true for codon UUG coding for leucine in internal positions. In some exceptional cases, AUU or AUA in Prokaryotes and ACG or UUG in Eukaryotes may also serve as initiation codons for the first methionine in the chain. The identification of the initiation codons, however, does not solve the starting point problem of the coding sequence. The difficulty is that by no means every AUG (the more so GUG or UUG) triplet becomes an initiation codon. Generally, translation cannot be initiated from internal AUG, GUG, or UUG triplets. If an mRNA chain is scanned from its 5'-end, AUG as well as GUG and UUG triplets may be found repeatedly both in frame with the subsequent coding sequence and out of frame, but they cannot initiate translation. Finally, many AUG, GUG, and UUG triplets located within the coding sequence but out of the reading frame fortunately do not initiate synthesis of erroneous polypeptides. Thus, in contrast to all other codons, both sense and nonsense ones, the choice of a given codon as an initiation point depends not only on the codon structure, i.e. its nucleotide composition and sequence, but also on the position of the codon in the mRNA. Certain structural elements in mRNA confer the capacity to serve as initiation codon to a given AUG (or GUG, or UUG). Specifically the nucleotide sequence preceding the initiation codon, as well as the particular secondary and tertiary structures of this mRNA region, are vital for the corresponding triplet to be exposed as an initiation codon (Chapter 15).

A given mRNA polynucleotide chain does not necessarily contain just one coding sequence. In prokaryotic mRNAs it is common for one polynucleotide chain to contain coding sequences for several proteins. Such mRNAs are usually called polycistronic mRNAs. (This term comes from the word cistron, which S. Benzer introduced as an equivalent of a gene). Different coding sequences (cistrons) within a given mRNA chain are usually separated by internal noncoding sequences. Such an internal noncoding sequence begins from the termination codon of the preceding cistron. The next cistron begins from an initiation codon such as AUG (or GUG).

In contrast to Prokaryotes, in eukaryotic organisms mRNAs are as a rule monocistronic, i.e. they code for just one polypeptide chain. The eukaryotic mRNA coding sequence is flanked both at the 5'-end and at the 3'-end by noncoding (untranslated) sequences (5'- and 3'-UTRs), the 3'-UTR being typically very long (comparable with the length of the coding sequence). It has already been mentioned that the vast majority of eukaryotic mRNAs have also poly(A) tracts of various length at the 3'-end. The 5'-end is usually modified by the cap (Fig. 2.4), which appears to be essential for the association between the mRNA and the ribosome prior to initiation.

It is appropriate to emphasize here that the mechanisms responsible for searching for the initiation codon in prokaryotic and eukaryotic translation systems are different. Prokaryotic ribosomes form a complex with mRNA and recognize the initiation Figure 2.4. Cap structure at the 5'-end of codon independently of the 5'-end; it is for this reason eukaryotic mRNA. that they can initiate from internal sites in the

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