Robert Wood Johnson Medical School
Dept. of Biochemistry & Molecular Biology
Piscataway, NJ 08854
Regulation of gene expression at the translational level, incorporation and utilization of selenocysteine
Our primary research question targets the protein synthetic machinery as one of the primary sites for the regulation of gene expression and an important sensor of the status of cellular metabolite concentrations. The utilization of selenium exemplifies this relationship, and is required for the synthesis and function of an essential group of proteins that contain the amino acid selenocysteine (Sec). In fact, many selenoproteins are known to provide protection from cellular damage and transformation, thus making the synthesis and regulation of these proteins an essential area of research. Sec is incorporated into these proteins by a translational recoding event at specific Stop (UGA) codons that are found upstream of stable stem-loop structures known as Sec insertion sequence (SECIS) elements. While the UGA codon and the SECIS element are the only known cis-acting elements required for Sec incorporation, at least two trans-acting factors are also required: 1) the Sec-specific elongation factor (eEFSec) and 2) a SECIS binding protein (SBP2). One of the ultimate goals for selenocysteine research is to be able to specifically regulate the expression of potentially beneficial selenoproteins in vivo. In order to achieve this goal, we must understand all of the factors that contribute not only to the basic Sec incorporation reaction but also to the regulation of this process. In addition to characterizing the structure and function of the known factors, much of our work is designed to test hypotheses regarding the identity and function of novel factors involved in the synthesis of selenoproteins utilizing both mammalian systems and plant-based systems.