Lodish model and regulation of ribosomal protein synthesis by insulin-deficient chick embryo fibroblasts

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Abstract
The production of ribosomal proteins in chick embryo fibroblasts that have been deprived of insulin is depressed to a much greater degree than that of most or all other cell proteins. Previous observations ruled out explanations for the preferential decrease in ribosomal protein formation that depend upon a selective destruction of ribosomal protein messages or a regulatory role for nascent rRNA. The proposition was now examined that ribosomal protein mRNA in the hormone-deficient chick embryo cells have a lower affinity for a limiting, early acting component of the initiating machinery than do most other cell messages and, in consequence, suffer from a translational disadvantage. The approach that was used depends upon the findings of Lodish and others that all mRNA are not initiated with equal ease, that inhibitors of elongation favor the initiation of low-affinity mRNA, and that agents that dampen an early step in initiation discriminate against the low-affinity messages. The idea was tested by comparing the effects of various inhibitors on the rates of synthesis of total cell protein and individual nonribosomal proteins with those of individual ribosomal proteins. The results fit the Lodish model and are consistent with the conclusions that ribosomal protein mRNA are more poorly initiated in the resting fibroblasts than are most or all other cell messages and that this condition is largely or entirely responsible for the low rate of ribosomal protein formation.