Translational Control Atlanta GA

The control of gene expression can also utilize translational mechanisms. These mechanisms are usually directed at initiation. For example, in response to virus challenge, the protein interferon is released and turns off protein synthesis in neighboring cells by a dual mechanism. First, interferon induces mRNA degradation. In response to interferon, an unusual RNA-related molecule, 2′,5′-oligoadenylic acid is made. This stimulates a cellular endonuclease, which degrades cellular RNA to inhibit cell growth. Thus, interferon is a mechanism to limit the damage from a virus infection. A double-stranded RNA cofactor is required for 2′,5′-ligoA synthesis. Cells don't usually have double-stranded RNA, but RNA viruses require double-stranded RNA for replication. This limits interferon-induced cell damage largely to virus-infected cells. Interferon also induces phosphorylation of eIF₂,which further inhibits initiation.

A similar mechanism operates in the control of globin mRNA translation. The production of heme and of globin must be closely coordinated, because hemoglobin contains exactly one heme and two each of the α- and β-globins. The major mRNAs in the developing red blood cell are those for the globin proteins. This means that changes in the activity of the ribosomes will affect globin production, primarily.

The translation of globin mRNA is dependent on free heme. The absence of heme leads to phosphorylation of eIF₂ through a hemin-controlled inhibitor. In the absence of heme, the hemin-controlled inhibitor protein is an active protein kinase, which phosphorylates eIF₂. When heme is again available, the hemin-controlled inhibitor binds heme and is inactivated, allowing protein synthesis to resume. See Figure 1 .

Figure 1

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