Characterization of Fragile X Mental Retardation Protein granules formation and dynamics in Drosophila
| Autor: | David Martel, Laetitia Coudert, Samia Mellaoui, Cristina Gareau, Rachid Mazroui |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Fragile x
congenital hereditary and neonatal diseases and abnormalities QH301-705.5 Science Single gene Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Stress granule Protein translation Biology (General) 030304 developmental biology Genetics 0303 health sciences RNA Cell biology nervous system diseases Cytosol FRAGILE X MENTAL RETARDATION SYNDROME RNA-Binding Motif General Agricultural and Biological Sciences FMRP 030217 neurology & neurosurgery Research Article |
| Zdroj: | Biology Open, Vol 2, Iss 1, Pp 68-81 (2012) Biology Open |
| ISSN: | 2046-6390 |
| Popis: | Summary FMRP is an evolutionarily conserved protein that is highly expressed in neurons and its deficiency causes fragile X mental retardation syndrome. FMRP controls the translation of target mRNAs in part by promoting their dynamic transport in neuronal RNA granules. We have previously shown that high expression of mammalian FMRP induces formation of granules termed FMRP granules. These RNA granules are reminiscent of neuronal granules, of stress granules, as well as of the recently described in vitro-assembled granules. In contrast with mammalian FMRP, which has two paralog proteins, Drosophila FMRP (dFMRP) is encoded by a single gene that has no paralog. Using this genetically simple organism, we investigated formation and dynamics of FMRP granules. We found that increased expression of dFMRP in Drosophila cells induces the formation of dynamic dFMRP RNA granules. Mutagenesis studies identified the N-terminal protein–protein domain of dFMRP as a key determinant for FMRP granules formation. The RGG RNA binding motif of dFMRP is dispensable for dFMRP granules formation since its deletion does not prevent formation of those granules. Deletion of the RGG motif reduced, however, dFMRP trafficking between FMRP granules and the cytosol. Similarly, deletion of a large part of the KH RNA binding motif of dFMRP had no effect on formation of dFMRP-granules, but diminished the shuttling activity of dFMRP. Our results thus suggest that the mechanisms controlling formation of RNA granules and those promoting their dynamics are uncoupled. This study opens new avenues to further elucidate the molecular mechanisms controlling FMRP trafficking with its associated mRNAs in and out of RNA granules. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|