Cited by 677Genetics and Neurodevelopmental DisordersRNA Research and SplicingRNA and protein synthesis mechanisms

The Fragile X Syndrome Protein FMRP Associates with BC1 RNA and Regulates the Translation of Specific mRNAs at Synapses

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Zalfa, Francesca, Giorgi, Marcello, Primerano, Beatrice, Moro, Annamaria, Di Penta, Alessandra, Reis, Surya, Oostra, Ben, Bagni, Claudia·2003·Cell

Abstract

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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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
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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