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The fragile X mental retardation protein has nucleic acid chaperone properties.

Publication Type:

Journal Article

Source:

Nucleic Acids Res, Volume 32, Issue 7, p.2129-37 (2004)

Keywords:

Amino Acid Motifs, DNA, Fragile X Mental Retardation Protein, Fragile X Syndrome, Humans, Intellectual Disability, Molecular Chaperones, Molecular Sequence Data, Nerve Tissue Proteins, Nucleic Acid Hybridization, RNA, RNA, Catalytic, RNA-Binding Proteins, Sequence Deletion, Substrate Specificity

Abstract:

<p>The fragile X syndrome is the most common cause of inherited mental retardation resulting from the absence of the fragile X mental retardation protein (FMRP). FMRP contains two K-homology (KH) domains and one RGG box that are landmarks characteristic of RNA-binding proteins. In agreement with this, FMRP associates with messenger ribonucleoparticles (mRNPs) within actively translating ribosomes, and is thought to regulate translation of target mRNAs, including its own transcript. To investigate whether FMRP might chaperone nucleic acid folding and hybridization, we analysed the annealing and strand exchange activities of DNA oligonucleotides and the enhancement of ribozyme-directed RNA substrate cleavage by FMRP and deleted variants relative to canonical nucleic acid chaperones, such as the cellular YB-1/p50 protein and the retroviral nucleocapsid protein HIV-1 NCp7. FMRP was found to possess all the properties of a potent nucleic acid chaperone, requiring the KH motifs and RGG box for optimal activity. These findings suggest that FMRP may regulate translation by acting on RNA-RNA interactions and thus on the structural status of mRNAs.</p>

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