Differential Gene Expression by Messenger RNA Competition
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Eukaryotic initiation factor 2 (eIF-2) has a dual function in initiation of protein synthesis: it binds Met-tRNAf to the small ribosomal subunit, and it binds directly to mRNA. The binding of eIF-2 to mRNA is highly specific and occurs in satellite tobacco necrosis virus RNA and Mengovirus RNA at the nucleotide sequences that constitute the ribosome binding sites. These findings support the concept that, during translation, eIF-2 may guide the ribosome to this site. Cl− or OAc− ions inhibit the direct binding of globin mRNA to eIP-2 in a manner that closely resembles their inhibitory effect on the translation of globin mRNA, an inhibition that is relieved by excess eIF-2. Hence,these anions may act to inhibit the interaction between mRNA and eIF-2 during protein synthesis. In mRNA-dependent reticulocyte lysates, a molecule of Mengovirus RNA competes in translation 35-fold more strongly than (on average) a molecule of globin mRNA. This competition is relieved by excess eIF-2. Mengovirus RNA binds directly to eIF-2 with 30-fold higher affinity than does globin mRNA. These results reveal a direct correlation between the affinity of a given mRNA species for eIF-2 and its ability to compete in translation. Indeed, the translational competition between α- and β-globin mRNA is also relieved by excess eIF-2, and in direct binding analysis, β-globin mRNA exhibits greater affinity for eIF-2 than does α-globin mRNA.
KeywordsMethyl Orange Differential Gene Expression Ribosomal Subunit Ribosome Binding Site mRNA Species
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