Classic genetic, biochemical, and recombinant DNA techniques are employed to study various aspects of translation. The experimental system is E. coli and some of its phages. The work explores the nature of ribosome binding sites and a large number of trans-acting proteins that compete with ribosomes for mRNA. The long-term objective is to fully appreciate the role played by translation and mRNA decay in determining the amount of a given gene product in a cell. Of the four major processes that determine the level of a given protein in a cell (transcription, splicing, translation, and mRNA decay), translation and mRNA decay receive limited attention from the community of research scientists. A second long-term goal is to understand the RNA CODE, the rules by which proteins recognize RNA molecules specifically and with high avidity. The work explores the contacts between RNA binding proteins and specific high affinity RNA ligands in detail. A major health relatedness of the work flows from the important human agents (including the AIDS virus) that use RNA genomes to accomplish their devastating activity. Experiments that pursue the means by which RNA interacts with proteins will, ultimately, provide rational drug therapies aimed at specific RNA genomes.
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