The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
The fragile X mental retardation protein inhibits translation via interacting with mRNA
Open accessAbstract
Fragile X syndrome is a frequent form of inherited mental retardation caused by functional loss of the fragile X mental retardation protein, FMRP. The function of FMRP is unknown, as is the mechanism by which its loss leads to cognitive deficits. Recent studies have determined that FMRP is a selective RNA-binding protein associated with polyribosomes, leading to the hypothesis that FMRP may be involved in translational regulation. Here we show that purified recombinant FMRP causes a dose-dependent translational inhibition of brain poly(A) RNA in rabbit reticulocyte lysate without accelerated mRNA degradation. In our translation reaction FMRP interacts with other messenger ribonucleoproteins and pre-exposure of FMRP to mRNA significantly increased the potency of FMRP as a translation inhibitor. Translation suppression by FMRP is reversed in a trans-acting manner by the 3'-untranslated portion of the Fmr1 message, which binds FMRP, suggesting that FMRP inhibits translation via interacting with mRNA. Consistently FMRP suppresses translation of the parathyroid hormone transcript, which binds FMRP, but not the beta-globin transcript, which does not bind FMRP. Moreover, removing the FMRP-binding site on a translation template abolishes the inhibitory effect of FMRP. Taken together, our results support the hypothesis that FMRP inhibits translation via interactions with the translation template.
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Cites
TRANSLATIONAL CONTROL IN MAMMALIAN CELLS
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FMR1 Protein: Conserved RNP Family Domains and Selective RNA Binding
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The protein product of the fragile X gene, FMR1, has characteristics of an RNA-binding protein.
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Evidence that fragile X mental retardation protein is a negative regulator of translation
Laggerbauer, B. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.4.329 · Cited by 571
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Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome
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Cited by
FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y. S., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.013 · Cited by 2,072
The mGluR theory of fragile X mental retardation
Bear, M. F., Huber, K. M., & Warren, S. T. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.04.009 · Cited by 1,580
Altered synaptic plasticity in a mouse model of fragile X mental retardation
Huber, K. M., Gallagher, S. M., Warren, S. T., & Bear, M. F. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122205699 · Cited by 1,349
Trinucleotide Repeat Disorders
Orr, H. T., & Zoghbi, H. Y. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.113042 · Cited by 1,368
Brown, V., Jin, P., Ceman, S., Darnell, J. C., O'Donnell, W. T., Tenenbaum, S. A., Jin, X., Feng, Y., Wilkinson, K. D., Keene, J. D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00568-2 · Cited by 1,109
Metadata
- Authors
- Li, Z.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-06-01
- Volume
- 29
- Issue
- 11
- Pages
- 2276-2283
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W2099503180
- Cited by
- 447
- References
- 37
- FWCI
- 16.05
- Type
- journal article
- Language
- en
- Open access
- bronze
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