After the RNA has been transported to the cytoplasm, it is translated into protein. Control of this process is largely dependent on the RNA molecule. As previously discussed, the stability of the RNA will have a large impact on its translation into a protein. As the stability changes, the amount of time that it is available for translation also changes.
The Initiation Complex and Translation Rate
Like transcription, translation is controlled by proteins that bind and initiate the process. In translation, the complex that assembles to start the process is referred to as the initiation complex. The first protein to bind to the RNA to initiate translation is the eukaryotic initiation factor-2 (eIF-2). The eIF-2 protein is active when it binds to the high-energy molecule guanosine triphosphate (GTP). GTP provides the energy to start the reaction by giving up a phosphate and becoming guanosine diphosphate (GDP). The eIF-2 protein bound to GTP binds to the small 40S ribosomal subunit. When bound, the methionine initiator tRNA associates with the eIF-2/40S ribosome complex, bringing along with it the mRNA to be translated.
At this point, when the initiator complex is assembled, the GTP is converted into GDP and energy is released. The phosphate and the eIF-2 protein are released from the complex and the large 60S ribosomal subunit binds to translate the RNA. The binding of eIF-2 to the RNA is controlled by phosphorylation. If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. Therefore, the initiation complex cannot form properly and translation is impeded (see the figure below). When eIF-2 remains unphosphorylated, it binds the RNA and actively translates the protein.
Art Connection
Gene expression can be controlled by factors that bind the translation initiation complex.
An increase in phosphorylation levels of eIF-2 has been observed in patients with neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s. What impact do you think this might have on protein synthesis?
Answer
Protein synthesis would be inhibited.