Translational control of gene expression in the human brain

1. Translational control is the regulation of protein synthesis as an alteration in the efficiency of mRNA translation and is a common mechanism by which cells regulate gene expression. 2. Alternations of total protein synthesis are often the responses of cells to various stress stimuli including starvation, viral infection, and heat shock. 3. Numerous specific genes including ferritin heavy chain, tubulin, vimentin and the lck proto-oncogene have also been shown to be under translational control. 4. Unlike cultured cells or intact organisms, the investigation of translational control in the human brain requires the measurement of components of protein synthesis, especially polysomes. Therefore, we have purified and characterized polysomes from human postmortem brain tissues and compared them to polysomes purified from the adult rat brain. 5. The yield (as A260 units per gram brain tissue), size (as number of ribosomes per message), translational efficiency (as amount protein synthesized per A260 unit), and ability to reinitiate (as amount of protein synthesis prevented by initiation inhibitors) were all significantly lower as exhibited by the human polysomes compared with the rat polysomes. However, the human and rat polysomes synthesized similar polypeptides. 6. Thus, the human polysomes differed from the rat polysomes principally in the efficiency of mRNA translation which is likely due to the greatly reduced ability of the human polysomes to initiate protein synthesis.