Eukaryotic mRNAs do not contain such a sequence. Instead, as discussed in Chapter 6, the selection of an AUG codon as a translation start site is largely determined by its proximity to the cap at the 5ʹ end of the mRNA molecule, which is the site at which the small ribosomal subunit binds to the mRNA and begins scanning for an initiating AUG codon. In eukaryotes, translational repressors can bind to the 5ʹ end of the mRNA and thereby inhibit translation initiation. Other repressors recognize nucleotide sequences in the 3ʹ UTR of specific mRNAs and decrease translation initiation by interfering with the communication between the 5ʹ cap and 3ʹ poly-A tail, a step required for efficient translation (see Figure 6–70). A particularly important type of translational control in eukaryotes relies on small RNAs (termed microRNAs or miRNAs) that bind to mRNAs and reduce protein output, as described later in this chapter.
the phosphorylation of an initiation factor regulates protein Synthesis Globally
Eukaryotic cells decrease their overall rate of protein synthesis in response to a variety of situations, including deprivation of growth factors or nutrients, infection by viruses, and sudden increases in temperature. Much of this decrease is caused by the phosphorylation of the translation initiation factor eIF2 by specific protein kinases that respond to the changes in conditions.
The normal function of eIF2 was outlined in Chapter 6. It forms a complex with GTP and mediates the binding of the methionyl initiator tRNA to the small ribosomal subunit, which then binds to the 5ʹ end of the mRNA and begins scanning along the mRNA. When an AUG codon is recognized, the eIF2 protein hydrolyzes the bound GTP to GDP, causing a conformational change in the protein and releasing it from the small ribosomal subunit. The large ribosomal subunit then joins the small one to form a complete ribosome that begins protein synthesis.
Figure 7–66 Mechanisms of translational control. Although these examples are from bacteria, many of the same principles operate in eukaryotes.
(A) Sequence-specific rnA-binding proteins repress translation of specific mrnAs by blocking access of the ribosome to the Shine–Dalgarno sequence (orange). for example, some ribosomal proteins repress translation of their own rnA. this mechanism allows the cell to maintain correctly balanced quantities of the various components needed to form ribosomes. (B) An rnA “thermosensor” permits efficient translation initiation only at elevated temperatures at which the stem-loop structure has been melted. An example occurs in the human pathogen Listeria monocytogenes, in which the translation of its virulence genes increases at 37°C, the temperature of the host. (C) Binding of a small molecule to a riboswitch causes a major rearrangement of the rnA forming a different set of stem-loop structures. in the bound structure, the Shine–Dalgarno sequence (orange) is sequestered and translation initiation is thereby blocked. in many bacteria, S-adenosylmethionine acts in this manner to block production of the enzymes that synthesize it. (D) An “antisense” rnA produced elsewhere from the genome base-pairs with a specific mrnA and blocks its translation. Many bacteria regulate expression of iron-storage proteins in this way.