Figure 15.7. Comparison of nucleotide sequences and secondary structures of the 3'-terminal regions of prokaryotic 16S and eukaryotic 18S ribosomal RNAs. The pyrimidine pentnucleotide insert ("anti-Shine-Dalgarno sequence") of the prokaryotic RNA is in black box (see the review by J. A. Steitz, in Ribosomes: Structure, Function, and Genetics, eds. G. Chambliss, G. R. Craven, J. Davies, K. Davis, L. Kahan, & M. Nomura, p.p. 479-495. University Park Press, Baltimore, 1980).

could be a more ancient mechanism, and the evolution of Prokaryotes, particularly the evolution of operons and polycistronic messages, could induce the appearance of a specialized mechanism for recognizing internal initiation regions; the pairing of the polypurine Shine-Dalgarno sequence of mRNA with the evolutionary acquired CCUCC insert near the 3'-end of the ribosomal 16S RNA is part of such a new mechanism).

15.3.2.The Cap Structure and the Initiation Codons

The cap (see Fig. 2.4) is added at the 5'-end of eukaryotic mRNAs during synthesis and processing of pre-mRNA in the nucleus. The cap structure takes a very important part in the initiation of translation. It is the cap structure that attracts initiation factors and ribosomes for the 5'-terminal initiation (see Fig. 15.1 A).

The cap is followed by the so-called 5'-untranslated region (5'-UTR) of mRNA. Typically the 5'-UTRs of eukaryotic mRNAs are not very long, up to several dozens nucleotides, although there are many exceptions. The cap and the adjacent section of the 5'-UTR form the ribosome-binding region (RBS) where the initiating 40S ribosomal subunit (43S initiation complex, see below) may bind. There is evidence that eukaryotic mRNAs lacking stable secondary structure in their 5'-UTRs display a higher initiation rate than those possessing such structures, and the inhibition of initiation by stable helical elements is more severe when they are close to the 5'-terminus (to the cap structure).

In contrast to Prokaryotes, the initiation codon in eukaryotic mRNAs is usually located some distance away from the RBS along the polynucleotide chain (Fig. 15.8). In order to reach the initiation codon from the RBS, the ribosomal initiation complex must move along the 5'-UTR downstream. According to the classical model of M. Kozak (1978, 1989b), in the process of the movement the initiation complex scans the sequence of mRNA until it encounters the triplet AUG; thus this triplet becomes the initiation codon. Indeed, in many eukaryotic mRNAs the first AUG triplet from the 5'-end is used as the initiation codon and thus establishes the reading frame of the subsequent sequence.

At the same time there are many cases where the first AUG triplet is not an initiation codon, but the initiation occurs at the second or the third (or the next) AUG, this being not necessarily in frame with the previous ones. The explanation is that the scanning ribosomal particles can skip some AUG triplets if they association 40S : elF's m7Gpp

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