TRANSLATIONAL CONTROL OF GENE EXPRESSION BY MRNA SELECTI

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Qualitative control of translation is an important mechanism for changing the relative abundancies of different proteins. It is achieved by selective regulation of mRNA binding to ribosomes and is a significant feature of the control of gene expression in animal cells. Such control is observed in the shut-off of host protein synthesis by viruses, in the maintenance of the differentiated state, in the response of cells to heat-shock and in the utilization of stored maternal mRNA during early development. Not only is this control of translation a means of short-term regulation of gene expression, but increasing evidence suggests that it may provide fine-tuning on transcription by feed-back inhibition. The mechanism whereby qualitative control is exerted is currently not understood. Conceivable mechanisms include: a) Non-specific changes in the overall rate of protein synthesis caused by changes in the availability of mRNAs, activated small ribosomal subunits, or initiation factors. b) Specific inhibition of mRNA binding to ribosomes by inhibitory factors or product feedback. c) Specific promotion of mRNA binding by stimulatory factors. The present proposal undertakes to study qualitative translational control using histone synthesis in sea urchin eggs and cleavage-stage embryos as a model system. Whether one or all of the above mechanisms are operative will be determined. The sea urchin system is chosen because histone synthesis is known to be subject to translational control and because there are indications that the system exhibits multiple types of mRNA selection processes. Different histone variants are synthesized at different developmental stages, suggestive of a role of the variants in the regulation of gene expression. In view of this, an understanding of translational control of the histone gene family will increase our comprenension of the regulatory mechanisms operative on gene expression during development.