|Understanding the function of fragile X protein in Drosophila: Characterization of dFMR1 and its associated molecules
by Haruhiko Siomi, 6/1/1999
Our genes make up the scaffolding upon which proteins are created. Each gene encodes for an "alphabet" that encodes for thousands of proteins. Many fragile X patients either fail to make the protein product of the fragile X gene, FMR1, or make an ineffective mutant version of it. In order for a protein to be produced, another chemical, RNA, must be created upon the DNA scaffolding of the gene. RNA is the cell's workhorse: it copies the genetic message off DNA and takes it out to the cellular factories (ribosomes) where the encoded message dictates the assembly of a protein. In normal cells, the FMR1 protein can bind RNA and is associated with ribosomes.
Interestingly, in our cells, there are two genetic "cousins" of FMR1, termed FXR1 and FXR2, which are thought to team up with and work together with FMR1. The current hypothesis is that the FMR1 and FXR proteins bind to specific messenger RNAs and regulate expression of those RNAs at ribosomes (protein assembly factories) in a manner critical for correct development of neurons in the brain. One of our goals is to sort through the thousands of RNAs that brain cells make and find the particular RNA that the FMR1 protein binds to. In order for this to be achieved, we plan to manipulate cells in such a way where they fail to make FMR1 and/or FXRs. We then will compare the expression of RNAs at ribosomes in cells that make the FMR1 and FXR proteins and the expression of RNAs in cells which fail to make these proteins. Once we elucidate these differences, we can effectively begin to address the question of how the lack of FMR1 expression (or the expression of mutated version of FMR1) leads to symptoms in fragile X syndrome.