Български
Research is sponsored fully by the Bulgarian Science Fund, Grant number DID 02/35
Short background
Fragile X is the most common form of inherited mental retardation in human caused by the loss of the fragile X mental retardation protein 1(FMRP).
A/ Drosophila has been used successfully as a model system to dissect genetic pathways implicated in fragile X syndrome. The Drosophila fragile X mental retardation protein 1(dFMRP1 or dFMRP) is involved in multiple aspects of neuronal development: axonal growth(and branching), synapse formation and dendritic branching(Xu et al., 2009).
B/ dFMRP is an RNA-binding protein which is found to be associated with the polysomes and is thought to function as a translational repressor of its mRNA targets (Ashley et al., 1993; O’Donnel et al., 2002; Jin and Warren, 2003).
C/ dFMRP1 is also implicated in the microRNA pathway (makes a complex with components of this pathway) and there is accumulating data suggesting that the protein executes its function in translation control by regulating different aspects of microRNAs metabolism processing efficiency and steady state level (Xu et al., 2009).
D/ dFMRP has also been shown to be a regulator of chromatin mediated epigenetic gene silencing. It is required for centric heterochromatin assembly during oogenesis (Deshpande et al., 2006).
E/ Besides its important functions in the brain, dFMRP was found to be a key protein, which is predicted to be involved in the expression control of many genes from a variety of biological processes – cell growth and cell division,differentiation, embryogenesis, development (Bauer et al., 2008).
F/ miRNAs are suggested to regulate chromatin structure by regulating key histone modifiers (Chuang and Jones, 2007).
This last group of data may present a possible link between miRNAs (posttranscriptional control) and epigenetic(transcriptional) control of gene expression.
Based on the above groups of facts we plan to carry out the following experiments.
We plan to identify some neurodevelopmental mRNA targets to which dFMRP supposedly directly binds and to study the expression control of dFMRP on these targets.
We also plan to look at the possible involvement of this protein in the expression control of other genes which might be mediated by by epigenetic chromatin remodeling.
