Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fragile X syndrome is one of the most common human genetic diseases and the most common cause of hereditary mental retardation. The gene that causes fragile X syndrome, FMR1, was recently identified and sequenced and found to encode a putative protein of unknown function. Here we report that FMR1 contains two types of sequence motifs recently found in RNA-binding proteins: an RGG box and two heterogeneous nuclear RNP K homology domains. We also demonstrate that FMR1 binds RNA in vitro. Using antibodies to FMR1, we detect its expression in divergent organisms and in cells of unaffected humans, but fragile X-affected patients express little or no FMR1. These findings demonstrate that FMR1 expression is directly correlated with the fragile X syndrome and suggest that anti-FMR1 antibodies will be important for diagnosis of fragile X syndrome. Furthermore, the RNA binding activity of FMR1 opens the way to understanding the function of FMR1.
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PMID:The protein product of the fragile X gene, FMR1, has characteristics of an RNA-binding protein. 768 65

Fragile-X syndrome, the most common monogenic form of mental retardation, is caused by down-regulation of the expression of Fragile X Mental Retardation Protein (FMRP). FMRP is a multifunctional, multidomain RNA-binding protein that acts as a translational repressor in neuronal cells. Interaction between FMRP and mRNA targets involves an RGG box, a protein motif commonly thought to mediate unspecific interactions with nucleic acids. Instead, FMRP RGG box has been shown to recognize RNA G-quartet structures specifically and to be necessary in neurons for RNP particle formation and dendritic mRNA localization. In the present study, we have characterized structurally three representative RNA targets of FMRP in their unbound form and in complex with the RGG box. We observe a large heterogeneity in the conformation of the RNA targets and in their RGG binding mode, which could be the basis of recognition specificity. We also found that G-quartet formation occurs not only intramolecularly but can also be mediated by RNA dimerization. These findings suggest a potential role of RNA:RNA interactions in protein:RNA complexes and in RNP particle assembly.
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PMID:G-quartet-dependent recognition between the FMRP RGG box and RNA. 1313 Jan 34

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.
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PMID:[The fragile X syndrome: one protein missing and 1001 disoriented mRNAs]. 1638 19

The Fragile X Mental Retardation protein (FMRP) is an RNA-binding protein and its absence leads to the Fragile X syndrome, the most common form of inherited mental retardation. Because it has been acknowledged for a long time that FMRP is associated with polyribosomal mRNPs in all non-neuronal cellular systems studied so far, it is thought that it regulates translation in neurons also; however, its exact function remains elusive. Recently, it has been reported that, contrary to non-neuronal cells, brain FMRP is not associated with the translation machinery, but is part of repressed small RNP complexes excluded from polyribosomes.(27) To elucidate this puzzling result, Stefani et al.(17) and Khandjian et al.(32) have optimized methods to analyze brain polyribosomes and now provide definitive evidence for the association of FMRP with brain polyribosomes. In addition, the data presented in these two reports clearly indicate that FMRP's function resides at the translation control level.
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PMID:Lost once, the Fragile X Mental Retardation protein is now back onto brain polyribosomes. 1713 37