Related Experiment Video
Updated: May 1, 2026
Dissecting Cell-Autonomous Function of Fragile X Mental Retardation Protein in an Auditory Circuit by In Ovo Electroporation
Published on: July 6, 2022
Fragile X mental retardation protein regulates translation by binding directly to the ribosome
Eileen Chen1, Manjuli R Sharma2, Xinying Shi1
1Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0314 USA.
Abstract:
Fragile X syndrome (FXS) is the most common form of inherited mental retardation, and it is caused by loss of function of the fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that is involved in the translational regulation of several neuronal mRNAs. However, the precise mechanism of translational inhibition by FMRP is unknown. Here, we show that FMRP inhibits translation by binding directly to the L5 protein on the 80S ribosome. Furthermore, cryoelectron microscopic reconstruction of the 80S ribosome⋅FMRP complex shows that FMRP binds within the intersubunit space of the ribosome such that it would preclude the binding of tRNA and translation elongation factors on the ribosome. These findings suggest that FMRP inhibits translation by blocking the essential components of the translational machinery from binding to the ribosome.
Insights
Fragile X syndrome (FXS) is linked to the fragile X mental retardation protein (FMRP). This study reveals FMRP inhibits translation by binding the 80S ribosome, blocking key components needed for protein synthesis.
Area of Science:
- Molecular Biology
- Genetics
- Neuroscience
Background:
- Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability.
- FXS results from the loss of function of the fragile X mental retardation protein (FMRP).
- FMRP, an RNA-binding protein, regulates neuronal mRNA translation, but its inhibitory mechanism is unclear.
Purpose of the Study:
- To elucidate the precise mechanism by which FMRP inhibits protein translation.
- To investigate the direct interaction of FMRP with the ribosome.
Main Methods:
- Biochemical assays to detect FMRP binding to ribosomal proteins.
- Cryo-electron microscopic reconstruction of the 80S ribosome-FMRP complex.
Main Results:
- FMRP directly binds to the L5 protein on the 80S ribosome.
- Cryo-EM reveals FMRP occupies the intersubunit space of the ribosome.
- FMRP binding obstructs the sites for tRNA and translation elongation factor attachment.
Conclusions:
- FMRP inhibits translation by physically blocking essential components of the translational machinery from accessing the ribosome.
- This provides a structural understanding of FMRP's role in translational repression in FXS.
More Related Videos
08:22A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene
Published on: September 16, 2019
10:59Analysis of Translation Initiation During Stress Conditions by Polysome Profiling
Published on: May 19, 2014
Related Concept Videos
01:23Regulation of Expression at Multiple Steps
01:29Translational Regulation
01:31Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
01:31Translation
Translation Produces the Building Blocks of Life
Proteins are...
02:24Regulation of Expression Occurs at Multiple Steps
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
01:23Transcriptional Regulation: Riboswitches