GENETICS AND BIOCHEMISTRY OF RIBOSOME BIOSYNTHESIS

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The ribosome, the organelle essential for protein synthesis, obviously plays a key role in cell growth and its regulation. In bacteria, the number of ribosomes in a cell is directly proportional to the growth rate of the cells under various culture conditions (except under conditions of very slow growth). The average rate of protein synthesis per ribosome in rapidly and slowly growing cells is the same, but the presence of more ribosomes in rich media permits more protein to be made and thus accounts for an overall increase in growth rate. Our goal is to understand how bacteria regulate the production of ribosomes and their growth rate. Specifically, our recent effort has focused on the identification of genes for ribosomal proteins and rRNA, and studies of the regulation of the expression of these important genes. We have recently discovered that ribosomal protein synthesis and ribosome assembly are coupled such that when ribosomal protein synthesis exceeds the rate of ribosome biosynthesis certain key ribosomal proteins act as inhibitors that prevent the further translation of their own mRNA. This feedback regulation model can account for coordinate and balanced synthesis of all of the ribosomal protein components. We will continue to study detailed mechanisms involved in the translational feedback regulation of ribosomal protein synthesis. In addition, we will study possible transcriptional regulation of ribosomal protein gene expression that might be operating as an important regulatory mechanism under some other conditions, e.g., during stringent control. Finally, we will study both in vivo and in vitro transcriptional regulation of rRNA gene expression which is fundamental to our understandig global regulation of ribosome accumulation in growing cells.