Translational Control of Apolipoprotein B mRNA

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We are proposing to study the biochemistry and cell biology of proteins important in lipid metabolism. Human liver secretes a number of proteins called "apolipoproteins" which are essential for formation of lipid particles called "lipoproteins". Secretion and metabolism of lipoproteins by the human liver is very important in maintaining the plasma levels of fat and cholesterol. We are interested in the basic molecular and cellular mechanisms which regulate the synthesis and secretion of these proteins. Our laboratory has been studying these mechanisms for the past several years and has made a number of important observations on regulation of apolipoprotein B synthesis. We now propose to continue these investigations to further elucidate key translational control mechanisms. Cells synthesize proteins by expressing their genes and making intermediate messenger molecules called "mRNA". The translation of the information on mRNA into a protein molecule is an important step at which protein expression is regulated. We have proposed to use a series of experiments to study the translation of the mRNA coding for apolipoprotein B. We will investigate the cellular factors which bind the mRNA and regulate its translation process. Structural elements within certain regions of an mRNA may interact with certain proteins within the cell. The protein factors involved in control of apoB mRNA translation will be studied over the next few years. We will also study the role of RNA-protein complexes called mRNPs as well as special cell granules called RNA granules. These complexes appear to store suppressed mRNA molecules which may be released upon metabolic stimulation for translation and protein synthesis. The long-term objective of this research program is to elucidate the cellular mechanisms which regulate the synthesis of apolipoproteins particularly apolipoprotein B by the human liver. The results will be useful in advancing our basic knowledge of how cells control their protein synthesis and expression.