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1 Origins and Targets of Translational Control

Michael B. Mathews, Nahum Sonenberg, John W.B. Hershey


The central idea of translational control proclaims that gene expression can be regulated by the efficiency of utilization of messenger RNA in specifying protein synthesis. This notion emerged only a few years after the articulation of the central dogma of molecular biology (Crick 1958) and very soon after the formulation of the messenger hypothesis. In 1961, Jacob and Monod perceived that “the synthesis of individual proteins may be provoked or suppressed within a cell, under the influence of specific external agents, and… the relative rates at which different proteins are synthesized may be profoundly altered, depending on external conditions.” They pointed out that such regulation “is absolutely essential to the survival of the cell,” and went on to advance the concept of an unstable RNA intermediary between gene and protein as a key feature of their elegant model for transcriptional control (Jacob and Monod 1961). The idea that this mRNA could be subject to differential utilization depending on the circumstances was accorded scant attention in the bacterial culture of the time, but it was taken up enthusiastically by workers in other fields, to the extent that 10 years later, one writer could allude to the “now classical conclusion” that eggs contain translationally silent mRNA that is activated upon fertilization (Humphreys 1971).

The term Translational Control was certainly in use as early as 1968, by which date at least four clearly distinct exemplars had been recognized and were already coming under mechanistic scrutiny. The groundwork for these...

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