Abstracts
Résumé
Le syndrome du X fragile, première cause de retard mental héréditaire, est une maladie monogénique liée au chromosome X. Le syndrome est causé par l’inactivation du gène Fragile Mental Retardation 1(FMR1) entraînant l’absence de la protéine FMRP dont le rôle présumé est de coordonner le devenir et la traduction d’un grand nombre d’ARNm. Toutefois, s’il est actuellement admis que FMRP se comporte comme un répresseur de la traduction dans certaines conditions expérimentales, et malgré les nombreuses publications sur le sujet, nous devons nous rendre à l’évidence que les fonctions réelles de FMRP sont encore mal connues. De plus, l’existence de deux protéines FXR1P et FXR2P, homologues à FMRP, suggère que la fonction de FMRP est bien plus complexe que celle imaginée à l’origine. Nous limitons les propos de cet article à l’état actuel des connaissances concernant le rôle de FMRP dans l’adressage des ARNm, ainsi qu’aux conséquences possibles de l’absence de FMRP sur le transport et la traduction des ARNm dans les cellules pourvues d’arborescences et de prolongements que sont les neurones.
Summary
Fragile X syndrome is the most common form of inherited mental retardation. This X-linked disease is due to transcriptional silencing of the Fragile Mental Retardation 1 (FMR1) gene and the absence of its gene product, FMRP. This protein is an RNA-binding protein present in mRNP complexes associated with the translation machinery and is thought to be a key player in the control of mRNA transport in neurons. However, the exact role of FMRP in translation remains unclear. Two homologous proteins, FXR1P and FXR2P, are also found in RNP complexes containing FMRP, suggesting that FMRP’s functions are much more complex than first thought. The molecular mechanisms altered in cells lacking FMRP still remain to be elucidated, as well as the putative roles of FXR1P and FXR2P as compensatory molecules. Here, we review the various possible functions of FMRP in RNA localization and transport in highly differentiated cells containing dendritic extensions such as neurons.
Appendices
Références
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