| What is FMRP and What Does It Do?
Fragile X syndrome occurs when the cells in a person do not produce FMRP (fragile X mental retardation protein). The image on the left is a diagrammatic representation of a portion of FMRP. The genetic code for how to synthesize FMRP is in the FMR1 (fragile X mental retardation 1) gene on the X
chromosome. Males have an X chromosome and a Y chromosome. Males with the stable FMR1 gene on their X chromosome make FMRP. Similarly, males with the premutation make FMRP. But males with the full FMR1 mutation do not make FMRP. Females have two X chromosomes. That means they have two copies of the FMR1 gene. Females who have the stable FMR1 on both of their X chromosomes make
FMRP. Females who have the premutation on one of their X chromosomes (and a stable version of FMR1 on the other X chromosome) make FMRP. Females who have the full FMR1 mutation on one of their X chromosomes (and a stable version of FMR1 on the other X chromosome) produce a reduced amount of FMRP. The major characteristics observed in individuals with fragile X syndrome are related to the
functioning of the brain. In addition, males with fragile X syndrome often have macroorchidism, enlarged testicles. Thus, it is not surprising that in individuals who do not have fragile X syndrome, the brain and testicles are places where the protein is actively synthesized. In other words, humans typically make FMRP in the testicles and the brain; if they can't, problems occur and we call those problems fragile X syndrome. There are also some other areas of the body that normally synthesize FMRP, such as the
liver, lung, kidney spinal cord, and gastrointestinal tract. These are not areas of significant problems for persons with fragile X syndrome. There are two other proteins, FXR1 and FXR2, which share some structural and functional characteristics with FMRP. It may be that in these tissues, FXR1 and FXR2 are able to compensate for a lack of FMRP. Obviously, FXR1 and FXR2 are not able to compensate for an absence of FMRP in the brains and testicles.We don't know exactly what the role of
FMRP is. There is evidence that it plays some role in regulating protein synthesis. Whatever the role of FMRP, it is not essential for survival but it is significant. In other words, if FMRP played a very minor role in cells, its absence would not cause a problem and there would be no disease called fragile X syndrome. Similarly, if FMRP was absolutely required for cells to function, no one missing the protein would survive birth and
again, there would be no fragile X syndrome. Instead, individuals who are missing FMRP survive, but with significant impacts on the quality of life. For further reading: (These are research articles written to communicate with other professionals.) - Bardoni, B., A. Schenck, et al. (1999).
"A novel RNA-binding nuclear protein that interacts with the fragile X mental retardation (FMR1) protein." Human Molecular Genetics 8(13): 2557-66. - Brown, V., K. Small, et al. (1998).
"Purified recombinant Fmrp exhibits selective RNA binding as an intrinsic property of the fragile X mental retardation protein." Journal of Biological Chemistry 273(25): 15521-15527. - Ceman, S., V. Brown, et al. (1999).
"Isolation of an FMRP-associated messenger ribonucleoprotein particle and identification of nucleolin and the fragile X-related proteins as components of the complex." Molecular and Cellular Biology 19(12): 7925-7932. - Corbin, F., M. Bouillon, et al. (1997).
"The fragile X mental retardation protein is associated with poly(A)+ mRNA in actively translating polyribosomes." Human Molecular Genetics 6(9): 1465-72. - Feng, Y., C. A. Gutekunst, et al. (1997).
"Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes." Journal of Neuroscience 17(5): 1539-1547. - Jin, P. and S. T. Warren (2000).
"Understanding the molecular basis of fragile X syndrome." Human Molecular Genetics 9(6): 901-8. - Kooy, R. F., R. Willemsen, et al. (2000).
"Fragile X syndrome at the turn of the century." Molecular Medicine Today 6(5): 193-8. - Tamanini, F., C. Bontekoe, et al. (1999).
"Different targets for the fragile X-related proteins revealed by their distinct nuclear localizations." Human Molecular Genetics 8(5): 863-9. - Zhong, N., W. Ju, et al. (1999).
"Reduced mRNA for G3BP in fragile X cells: evidence of FMR1 gene regulation." American Journal of Medical Genetics 84(3): 268-71
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