ERIC Number: EJ904409
Record Type: Journal
Publication Date: 2004-Feb
Abstractor: As Provided
Reference Count: 82
RNA Interference: A New Mechanism by Which FMRP Acts in the Normal Brain? What Can Drosophila Teach Us?
Siomi, Haruhiko; Ishizuka, Akira; Siomi, Mikiko C.
Mental Retardation and Developmental Disabilities Research Reviews, v10 n1 p68-74 Feb 2004
Fragile X syndrome is the most common heritable form of mental retardation caused by loss-of-function mutations in the "FMR1" gene. The "FMR1" gene encodes an RNA-binding protein that associates with translating ribosomes and acts as a negative translational regulator. Recent work in "Drosophila melanogaster" has shown that the fly homolog of "FMR1" ("dFMR1") plays an important role in regulating neuronal morphology, which may underlie the observed deficits in behaviors of "dFMR1" mutant flies. Biochemical analysis has revealed that dFMR1 forms a complex that includes ribosomal proteins and, surprisingly, Argonaute2 (AGO2), an essential component of the RNA-induced silencing complex (RISC) that mediates RNA interference (RNAi) in "Drosophila". dFMR1 also associates with Dicer, another essential processing enzyme of the RNAi pathway. Moreover, both a micro-RNA (miRNA) and short interfering RNAs (siRNAs) can coimmunoprecipitate with dFMR1. Together these findings suggest that dFMR1 functions in an RNAi-related apparatus to regulate the expression of its target genes at the level of translation. These findings raise the possibility that Fragile X syndrome may be the result of a protein synthesis abnormality caused by a defect in an RNAi-related apparatus. Because the core mechanisms of complex behaviors such as learning and memory and circadian rhythms appear to be conserved, studies of Fragile X syndrome using "Drosophila" as a model provide an economy-of-scale for identifying biological processes that likely underlie the abnormal morphology of dendritic spines and behavioral disturbances observed in Fragile X patients. (Contains 2 figures.)
Descriptors: Mental Retardation, Genetics, Biology, Brain, Genetic Disorders, Animals, Symptoms (Individual Disorders), Cognitive Ability, Behavior Problems
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Publication Type: Journal Articles; Reports - Evaluative
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