Question

In eukaryotes: what is the difference between the regulation of general versus specific translation? Describe one regulatory mechanism per each type.

Answer 1

The difference between general and specific translation in eukaryotes is that general regulation involves changes in the activity of eukaryotic initiation factors (eIFs) that would typically affect all cellular protein synthesis while specific regulation involves binding sequences or regions on one or a few mRNAs that recognize and bind specific regulatory proteins or other molecules.

The inhibition of ferritin translation by iron regulatory proteins is an example of specific regulatory mechanism of translation. Normally, the initiation complex scans the 5’-UTR of an mRNA. When it finds the normal translation start site, it can bind the large subunit and begin translating the polypeptide. In iron-deficient cells, scanning by the initiation complex is thought to be physically blocked by steric hindrance.

The regulation of globin mRNA translation initiation by hemin is an example of general regulatory mechanism of translation. When globin and heme levels become approximately equimolar, hemin is no longer in excess. It then dissociates from the active HCR kinase. The now- active kinase catalyzes eIF2B phosphorylation. Phospho-eIF2B is inactive, and cannot facilitate the GTP/GDP swap on eIF2. Globin mRNA translation initiation, thus blocked, allows a lower rate of globin polypeptide translation to keep pace with heme synthesis.