The regulation of ferritin mRNA translation in mammalian cells by iron will be investigated in detail. Attention will be focused on two recently identified components, the iron responsive sequence element within the 5' UTR of the mRNA, and the repressor. The mechanisms by which these interact to inhibit translation of ferritin mRNA will be defined. The possible roles of additional factors (loosely defined as "co- repressors") or additional elements of mRNA sequences and structure in the repression process will also be investigated. Finally, the mechanism by which iron causes the de-repression of mRNA translation will be explored. The results of these projects, if successful, will completely define the mechanisms by which ferritin translation is regulated. While this represents the first and best characterized example of translational induction/repression in eukaryotes, it is clearly by no means unique. Previous investigations have indicated the existence of many other genes whose expression appears to be similarly regulated. Perhaps this work will serve as a model system which will be generally useful in guiding explorations of other translationally regulated systems. Dr. Thach has done some very good on initiation factor functions which makes him well qualified for these studies.
