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The Fragile X Syndrome Protein FMRP Associates with BC1 RNA and Regulates the Translation of Specific mRNAs at Synapses
Open accessAbstract
The Fragile X syndrome, which results from the absence of functional FMRP protein, is the most common heritable form of mental retardation. Here, we show that FMRP acts as a translational repressor of specific mRNAs at synapses. Interestingly, FMRP associates not only with these target mRNAs, but also with the dendritic, non-translatable RNA BC1. Blocking of BC1 inhibits the interaction of FMRP with its target mRNAs. Furthermore, BC1 binds directly to FMRP and can also associate, in the absence of any protein, with the mRNAs regulated by FMRP. This suggests a mechanism where BC1 could determine the specificity of FMRP function by linking the regulated mRNAs and FMRP. Thus, when FMRP is not present, loss of translational repression of specific mRNAs at synapses could result in synaptic dysfunction phenotype of Fragile X patients.
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“This protein negatively regulates the translation of specific mRNAs at the synapse23,54.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [54]
In the citing paper
“Absence of FMRP leads to an increase of local protein synthesis (Figures 2 and 3), initially shown for the activity-regulated cytoskeleton protein (Arc), microtubule-associated protein 1B (Map1B), and alpha Ca 2+ /calmodulin-dependent kinase II (αCaMKII) proteins (69).”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [69]
In the citing paper
“As in oligomer-exposed neurons, neurons in Fragile X ectopically overexpress Arc (Zalfa et al., 2003).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Zalfa et al., 2003
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Metadata
- Authors
- Zalfa, F., Giorgi, M., Primerano, B., Moro, A., Di Penta, A., Reis, S., Oostra, B., & Bagni, C.
- Affiliations
- University of Rome Tor Vergata (IT)
- Erasmus MC (NL)
- Corresponding author
- Bagni, Claudia
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 112
- Issue
- 3
- Pages
- 317-327
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2002364516
- Cited by
- 676
- References
- 65
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 14 · 2023: 13 · 2022: 9 · 2021: 21 · 2020: 19 · 2019: 27 · 2018: 28 · 2017: 36 · 2016: 19 · 2015: 33 · 2014: 39 · 2013: 31 · 2012: 36
- FWCI
- 26.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Lirias (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R01 HD 38038, R01HD038038)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- fragile X syndrome, FMRP, BC1 RNA, protein synthesis inhibition, synaptic dysfunction, intellectual disability, RNA-binding proteins
- MeSH terms
- Animals, Base Sequence, Brain, Dendrites, Fragile X Syndrome, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Synaptic Transmission, Protein Binding, Ribonucleoproteins, RNA, Messenger, Synapses, Protein Biosynthesis, Tumor Cells, Cultured, Molecular Structure, Genes, Suppressor, RNA-Binding Proteins, Mice, Knockout, RNA, Small Cytoplasmic, Macromolecular Substances, Mice, Fragile X Messenger Ribonucleoprotein 1
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