Figure 6–70 The initiation of protein synthesis in eukaryotes. Only three eIF2 of the many translation initiation factors required for this process are shown. Efficient translation initiation also requires the poly-A tail of the mRNA bound by poly-A-binding proteins, which, in turn, interact with eIF4G (see Figure 6–38). In this way, the translation apparatus ascertains that both ends of the mRNA are intact before initiating protein synthesis. Although only one
GTP-hydrolysis event is shown in the figure, a second is known to occur subunit with just before the large and small ribosomal subunits join. In the last two steps initiator tRNA shown in the figure, the ribosome has begun the standard elongation cycle, bound to P site depicted in Figure 6–64.
helicases facilitate this movement. In 90% of mRNAs, translation begins at the first
AUG encountered by the small subunit. At this point, the initiation factors dis sociate, allowing the large ribosomal subunit to assemble with the complex and complete the ribosome. The initiator tRNA remains at the P site, leaving the A site vacant. Protein synthesis is therefore ready to begin (see Figure 6–70).
The nucleotides immediately surrounding the start site in eukaryotic mRNAs influence the efficiency of AUG recognition during the above scanning process. If this recognition site differs substantially from the consensus recognition sequence (5ʹ-ACCAUGG-3ʹ), scanning ribosomal subunits will sometimes ignore the first
AUG codon in the mRNA and skip to the second or third AUG codon instead. Cells frequently use this phenomenon, known as “leaky scanning,” to produce two or more proteins, differing in their N-termini, from the same mRNA molecule. This mechanism allows some genes to produce the same protein with and without a signal sequence attached at its N-terminus, for example, so that the protein is directed to two different compartments in the cell.
rial mRNAs have no 5ʹ caps to signal the ribosome where to begin searching for the start of translation. Instead, each bacterial mRNA contains a specific ribo- some-binding site (called the Shine–Dalgarno sequence, named after its discov-DISSOCIATE erers) that is located a few nucleotides upstream of the AUG at which translation
The mechanism for selecting a start codon in bacteria is different. Bacte is to begin. This nucleotide sequence, with the consensus 5ʹ-AGGAGGU-3ʹ, forms base pairs with the 16S rRNA of the small ribosomal subunit to position the initiating AUG codon in the ribosome. A set of translation initiation factors orchestrates this interaction, as well as the subsequent assembly of the large ribosomal subunit to complete the ribosome.
Unlike a eukaryotic ribosome, a bacterial ribosome can readily assemble directly on a start codon that lies in the interior of an mRNA molecule, so long as a ribosome-binding site precedes it by several nucleotides. As a result, bac-AMINOACYL terial mRNAs are often polycistronic—that is, they encode several different pro teins, each of which is translated from the same mRNA molecule (Figure 6–71). In contrast, a eukaryotic mRNA generally encodes only a single protein, or more accurately, a single set of closely related proteins.
Stop Codons Mark the End of Translation