G-quartet-dependent recognition between the FMRP RGG box and RNA
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Updated: Sep 18, 2026

Sample Preparation for Mass Spectrometry-based Identification of RNA-binding Regions
Published on: September 28, 2017
Andres Ramos1, David Hollingworth, Annalisa Pastore
1National Institute for Medical Research, London NW7 1AA, UK.
Abstract:
Fragile-X syndrome, the most common monogenic form of mental retardation, is caused by down-regulation of the expression of Fragile X Mental Retardation Protein (FMRP). FMRP is a multifunctional, multidomain RNA-binding protein that acts as a translational repressor in neuronal cells. Interaction between FMRP and mRNA targets involves an RGG box, a protein motif commonly thought to mediate unspecific interactions with nucleic acids. Instead, FMRP RGG box has been shown to recognize RNA G-quartet structures specifically and to be necessary in neurons for RNP particle formation and dendritic mRNA localization. In the present study, we have characterized structurally three representative RNA targets of FMRP in their unbound form and in complex with the RGG box. We observe a large heterogeneity in the conformation of the RNA targets and in their RGG binding mode, which could be the basis of recognition specificity. We also found that G-quartet formation occurs not only intramolecularly but can also be mediated by RNA dimerization. These findings suggest a potential role of RNA:RNA interactions in protein:RNA complexes and in RNP particle assembly.
Insights
Fragile X syndrome is linked to FMRP protein dysfunction. This study reveals how FMRP
Area of Science:
- Molecular Biology
- Neuroscience
- Genetics
Background:
- Fragile X syndrome, a common genetic cause of intellectual disability, results from reduced Fragile X Mental Retardation Protein (FMRP).
- FMRP is an RNA-binding protein crucial for translational repression in neurons, impacting mRNA regulation.
- The RGG box of FMRP is key for its interaction with RNA targets, specifically recognizing G-quartet structures.
Purpose of the Study:
- To structurally characterize FMRP RGG box interactions with its RNA targets.
- To investigate the structural basis of RNA recognition specificity by FMRP.
- To explore the role of RNA structure and potential RNA:RNA interactions in RNP assembly.
Main Methods:
- Structural characterization of three representative FMRP RNA targets in unbound and FMRP RGG box-bound states.
- Analysis of RNA conformation and binding modes using biophysical techniques (details not specified in abstract).
Main Results:
- Observed significant heterogeneity in the conformations of RNA targets and their binding modes with the FMRP RGG box.
- Demonstrated that G-quartet formation can occur through intramolecular folding or RNA dimerization.
- These structural variations suggest a basis for specific RNA recognition by FMRP.
Conclusions:
- FMRP RGG box binding specificity is potentially linked to diverse RNA conformations and binding modes.
- RNA dimerization-mediated G-quartet formation highlights the role of RNA:RNA interactions in complex formation.
- Findings suggest RNA:RNA interactions are important for protein:RNA complex assembly and RNP biogenesis in neurons.
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