Genetics - A. V. Sivolob 2008

Gene Expression
Gene expression in eukaryotes
Features of protein synthesis in eukaryotes

A generalized structural diagram of a mature eukaryotic mRNA released from the polymerase complex, transported to the Cytoplasm, and used as a template for Protein Synthesis is shown in Fig. 2.14. Between the cap and the beginning of the coding region (the start codon) lies the 5'-untranslated region (5' UTR). Downstream of the coding region, which ends with one of the stop codons, and upstream of the polyA sequence is the 3'-untranslated region. Both of these regions contain important sequence elements involved in the Regulation of Protein Synthesis.

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Fig. 2.14. Diagram of mRNA Structure

Each eukaryotic mRNA molecule contains only a single reading frame (one start codon); Components of the Translation initiation system in the cytoplasm initially interact with the cap at the 5' end of the molecule, followed by scanning of the template to locate the start codon (unlike prokaryotes, initiation occurs via a so-called scanning mechanism). The first encountered AUG codon is not necessarily recognized as the start codon. Start codon recognition depends on the sequence context in which it resides. The optimal context that maximally promotes translation initiation is the Kozak consensus sequence (Marilyn Kozak): GCC(A/G)CCAUGG. Accordingly, deviations from this context hinder the recognition of the start site and necessitate positive regulation of translation initiation. Initiation efficiency also depends on: the distance of the start codon from the 5' end of the mRNA—extended scanning during initiation increases the probability of complex dissociation; the presence or absence of double-stranded hairpins in the 5' UTR that impede the scanning process; and the presence or absence of regulatory Proteins or microRNA molecules (see below) that bind within the 5'-terminal region.

Translation elongation is likewise a target for regulatory control: the presence of hairpins within the coding region of the mRNA impedes elongation, as do repressors that recognize specific mRNA sequence elements. Altering mRNA half-life represents yet another pathway for regulating Gene Expression. The lifespan of mRNA in the cytoplasm depends primarily on the degree of protection of its 3' end against exonucleases (since the cap is resistant to Nucleases). Additional protection is conferred by proteins that bind to the 3' untranslated region—the absence of such binding leads correspondingly to rapid degradation.