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

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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

DOI 10.1016/s0092-8674(03)00079-5

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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
ORCID: Zalfa, Francesca
Reis, Surya
Bagni, Claudia
Venue: Cell
Publisher: Elsevier BV
Published: 2003-02
Volume: 112
Issue: 3
Pages: 317-327
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/s0092-8674(03)00079-5
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3819 d)
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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The Fragile X Syndrome Protein FMRP Associates with BC1 RNA and Regulates the Translation of Specific mRNAs at Synapses

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