Fragile X related protein 1 isoforms differentially modulate the affinity of fragile X mental retardation protein for G-quartet RNA structure

• Published in: Nucleic acids research Vol. 35; no. 1; pp. 299 - 306
• Main Authors: Bechara, Elias, Davidovic, Laetitia, Melko, Mireille, Bensaid, Mounia, Tremblay, Sandra, Grosgeorge, Josiane, Khandjian, Edouard W, Lalli, Enzo, Bardoni, Barbara
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-01-2007
• Subjects: Amino Acid Sequence; Biochemistry, Molecular Biology; Cancer; Fragile X Mental Retardation Protein; Fragile X Mental Retardation Protein - metabolism; Human health and pathology; Kinetics; Life Sciences; Molecular Sequence Data; Nucleic Acid Conformation; Protein Isoforms; Protein Isoforms - metabolism; RNA; RNA - chemistry; RNA - metabolism; RNA-Binding Proteins; RNA-Binding Proteins - chemistry; RNA-Binding Proteins - metabolism
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkl1021

Fragile X syndrome, the most frequent form of inherited mental retardation, is due to the absence of expression of the Fragile X Mental Retardation Protein (FMRP), an RNA binding protein with high specificity for G-quartet RNA structure. FMRP is involved in several steps of mRNA metabolism: nucleocytoplasmic trafficking, translational control and transport along dendrites in neurons. Fragile X Related Protein 1 (FXR1P), a homologue and interactor of FMRP, has been postulated to have a function similar to FMRP, leading to the hypothesis that it can compensate for the absence of FMRP in Fragile X patients. Here we analyze the ability of three isoforms of FXR1P, expressed in different tissues, to bind G-quartet RNA structure specifically. Only the longest FXR1P isoform was found to be able to bind specifically the G-quartet RNA, albeit with a lower affinity as compared to FMRP, whereas the other two isoforms negatively regulate the affinity of FMRP for G-quartet RNA. This result is important to decipher the molecular basis of fragile X syndrome, through the understanding of FMRP action in the context of its multimolecular complex in different tissues. In addition, we show that the action of FXR1P is synergistic rather than compensatory for FMRP function.