Abstract:
Control of protein synthesis in eukaryotic cells was studied by using two models: the c-myc oncogene and the translational transactivation of the human immunodeficiency virus (HIV) mRNAs. These two models are examples of control of expression of specific genes at the translation level. It was shown that the presence of the 5' noncoding regions of the human and murine c-myc oncogenes strongly inhibits the in vitro translation of their respective mRNAs. The presence of the 5' noncoding region of the mouse c-myc gene is sufficient by itself to reduce the translational efficiencies of messages since, when it is placed at the 5' end of coding sequences, it also reduces the translational level of these messages to similar levels observed with c-myc. Secondary structure at the level of the 5' end noncoding region might be the origin of the observed inhibition since this has been shown to be a determinant in translational efficiency. There was, however, no correlation between the results obtained from in vitro translation systems and observations made in cells transfected with genes containing the inhibitory region at their 5' end. The presence of the HIV mRNAs TAR sequence at the 5' end of the hybrid CAT message also reduces the in vitro translational efficiency of this mRNA. No transactivational activity in the presence of the tat III protein could be observed in the in vitro translation systems that were used in these studies. However, the cross-linking of an 80 kD polypeptide (most likely eIF-4B) to the mRNA cap structure was enhanced by the presence of the TAR region at the 5' end of hybrid messages. Moreover, cross-linking of a novel set of proteins to the cap structure of hybrid mRNA with the TAR sequence at the 5' end was detected in HeLa cells transfected with the tat III gene and expressing the transactivation activity in vivo. These results suggest that the c-myc oncogene and the transactivation of the HIV mRNAs might be in part regulated at the level of translation.
Keywords: Cell Line Gene Expression Regulation Human HIV/*GENETICS HIV Antigens/*GENETICS Proteins/*BIOSYNTHESIS Proto-Oncogene Proteins/*GENETICS *Proto-Oncogenes RNA, Messenger/GENETICS *Translation, Genetic THESIS
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