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PMID:19166269

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Citation

Bechara, EG, Didiot, MC, Melko, M, Davidovic, L, Bensaid, M, Martin, P, Castets, M, Pognonec, P, Khandjian, EW, Moine, H and Bardoni, B (2009) A novel function for fragile X mental retardation protein in translational activation. PLoS Biol. 7:e16

Abstract

Fragile X syndrome, the most frequent form of inherited mental retardation, is due to the absence of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in several steps of RNA metabolism. To date, two RNA motifs have been found to mediate FMRP/RNA interaction, the G-quartet and the "kissing complex," which both induce translational repression in the presence of FMRP. We show here a new role for FMRP as a positive modulator of translation. FMRP specifically binds Superoxide Dismutase 1 (Sod1) mRNA with high affinity through a novel RNA motif, SoSLIP (Sod1 mRNA Stem Loops Interacting with FMRP), which is folded as three independent stem-loop structures. FMRP induces a structural modification of the SoSLIP motif upon its interaction with it. SoSLIP also behaves as a translational activator whose action is potentiated by the interaction with FMRP. The absence of FMRP results in decreased expression of Sod1. Because it has been observed that brain metabolism of FMR1 null mice is more sensitive to oxidative stress, we propose that the deregulation of Sod1 expression may be at the basis of several traits of the physiopathology of the Fragile X syndrome, such as anxiety, sleep troubles, and autism.

Links

PubMed PMC2628407 Online version:10.1371/journal.pbio.1000016

Keywords

Animals; Binding Sites; Brain/enzymology; Fragile X Mental Retardation Protein/genetics; Fragile X Mental Retardation Protein/metabolism; Fragile X Syndrome/genetics; Gene Expression Regulation; Humans; Mice; Mice, Mutant Strains; Polyribosomes; Protein Biosynthesis; RNA, Messenger/chemistry; RNA, Messenger/metabolism; Superoxide Dismutase/genetics; Superoxide Dismutase/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:FMR1

enables

GO:0035613: RNA stem-loop binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:FMR1

enables

GO:0048027: mRNA 5'-UTR binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:FMR1

involved_in

GO:0045727: positive regulation of translation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FMR1

GO:0045727: positive regulation of translation

ECO:0000315:

P

Fig. 6: Sod1 expression reduced in Fmr1-mutant cells

complete
CACAO 6772

MOUSE:FMR1

involved_in

GO:0045727: positive regulation of translation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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