With a $95,000 grant from FRAXA Research Foundation from 2006-2007, Dr. Mihaela Mihailescu and her team at Dusquesne University studied the relationship between FMRP, RNA sequences, and G quartet structure. Results published.
by Mihaela Mihailescu, 4/1/2007
This project focuses on the investigation of the fragile X protein’s interactions with its mRNA targets. FMRP is thought to act as a translational repressor of specific messenger RNAs (mRNA;) in other words, FMRP keeps mRNA from being translated into protein until the appropriate signal occurs, indicating the right time to make that particular protein. Although the RNA targets of the protein remain elusive, it has been reported that FMRP binds to RNA sequences that have the potential to fold into structures called G quartets. Several studies strongly suggest that the microtubule associated protein 1B (MAP1B) mRNA is a potential target of FMRP.
The first specific aim of this study is to investigate to what extent phosphorylation and protein arginine methylation play a role in modulating the interactions of FMRP with its in vivo RNA targets, such as MAP1B RNA. Given the fact that the function of FMRP is mediated through its RNA binding activity, it is clearly relevant to determine if this activity is influenced by these posttranslational modifications, as they might act as regulatory signals for FMRP function.
The second specific aim of this study is to do a comparative analysis of the FMRP isoforms 1, 2, 3 interactions with MAP1B RNA, in order to determine at the molecular level to what extent the sequence modifications near the RGG box affect FMRP interactions with specific RNA targets.
Detailed study at the molecular level of the FMRP-RNA interactions (in particular FMRP-MAP1B RNA interactions) will contribute to our understanding of FMRP function and might lead to the identification of chemical compounds that could compensate for this function.