FRAXA Research Foundation funded a 2016 grant of $90,000 over two years for a postdoctoral fellowship for Thomas Maurin, PhD, who is working under the mentorship of Dr. Barbara Bardoni at INSERM in France. This project has been renewed in 2017 for a second year. The team works on the biochemistry of the fragile X protein.
The fragile X protein (FMRP) does not work alone. FMRP is present in particles which contain many other proteins, and the composition of these particles can vary significantly. Understand the protein partners of FMRP and their roles in shaping the different normal functions of FMRP is the primary interest of the Bardoni lab.
FMRP is a RNA-binding protein containing at least three domains mediating its binding to RNA (two KH domains and one RGG box) and it appears to be implicated in several steps of mRNA metabolism. These properties suggest that it is likely a component of different complexes, whose identification will result in a more precise dissection of FMRP function.
We plan to use sucrose gradient fractionation and FPLC chromatography with the purpose to perform a detailed analysis of FMRP-containing complexes in cultured cell lines and mouse brain, taking into consideration the composition and the dynamics of FMRP-containing complexes, the expression of FMRP-interacting proteins and, as a more long term project, the expression level of mRNAs that are targets of FMRP.
Another important point is to clearly elucidate the anatomy of the FMRP/mRNA complex at the molecular level. During the last four years, many putative RNA targets for FMRP have been identified. However, up to date, it has been reported that FMRP binds only two structures (G-quartet and kissing complex RNA) and a sequence (poly(U) stretch). We propose here a novel approach to identify sequence and/or structures, other than purine-quartet, that are recognized and bound by FMRP.