In resting T-lymphocytes and 3T3 fibroblasts, the mRNAs encoding the ribosomal proteins (r-protein) are strongly repressed; approximately 80% of each message is located in untranslated ribonucleo-protein particles under these conditions. Very rapidly after mitogenic stimulation, the cytosolic distribution of these MRNAs is changed, with the majority of the messages now translated in polysomes. The translational shift and the be resulting elevation in the synthesis of the r-proteins is one component of the increase in protein synthesis which is required for a cell to progress through the cell cycle to division. Our long-term goal is to elucidate the molecular details of this important translational control mechanism and to understand how this regulatory pathway is controlled by a mitogenic signal. The specific objectives of this proposal are to first determine the mRNA structures which are required for the translational regulation of the r-proteins. Using these sequences as a tool, we will identify and characterize translational factors and mRNA-binding proteins which may be involved in the growth regulation of these mRNAs. To understand how the activity of the transacting factors is modulated by growth factor/receptor interaction we will investigate the effects of altering known mitogen-induced signaling pathways on the translational shift of the r-protein mRNA.
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