FRAXE-associated mental retardation protein (FMR2) is an RNA-binding protein with high affinity for G-quartet RNA forming structure

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dc.contributor.authorBensaid, M.
dc.contributor.authorMelko, M.
dc.contributor.authorBechara, E.
dc.contributor.authorDavidovic, L.
dc.contributor.authorBerretta, A.
dc.contributor.authorCatania, M.
dc.contributor.authorGecz, J.
dc.contributor.authorLalli, E.
dc.contributor.authorBardoni, B.
dc.date.issued2009
dc.description.abstractFRAXE is a form of mild to moderate mental retardation due to the silencing of the FMR2 gene. The cellular function of FMR2 protein is presently unknown. By analogy with its homologue AF4, FMR2 was supposed to have a role in transcriptional regulation, but robust evidences supporting this hypothesis are lacking. We observed that FMR2 co-localizes with the splicing factor SC35 in nuclear speckles, the nuclear regions where splicing factors are concentrated, assembled and modified. Similarly to what was reported for splicing factors, blocking splicing or transcription leads to the accumulation of FMR2 in enlarged, rounded speckles. FMR2 is also localized in the nucleolus when splicing is blocked. We show here that FMR2 is able to specifically bind the G-quartet-forming RNA structure with high affinity. Remarkably, in vivo, in the presence of FMR2, the ESE action of the G-quartet situated in mRNA of an alternatively spliced exon of a minigene or of the putative target FMR1 appears reduced. Interestingly, FMR1 is silenced in the fragile X syndrome, another form of mental retardation. All together, our findings strongly suggest that FMR2 is an RNA-binding protein, which might be involved in alternative splicing regulation through an interaction with G-quartet RNA structure.
dc.description.statementofresponsibilityMounia Bensaid, Mireille Melko, Elias G. Bechara, Laetitia Davidovic, Antonio Berretta, Maria Vincenza Catania, Jozef Gecz, Enzo Lalli, and Barbara Bardoni
dc.identifier.citationNucleic Acids Research, 2009; 37(4):1269-1279
dc.identifier.doi10.1093/nar/gkn1058
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.orcidGecz, J. [0000-0002-7884-6861]
dc.identifier.urihttp://hdl.handle.net/2440/52685
dc.language.isoen
dc.publisherOxford Univ Press
dc.source.urihttps://doi.org/10.1093/nar/gkn1058
dc.subjectCells, Cultured
dc.subjectCell Line
dc.subjectCell Nucleus Structures
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectRNA-Binding Proteins
dc.subjectNuclear Proteins
dc.subjectRNA
dc.subjectAlternative Splicing
dc.subjectProtein Structure, Tertiary
dc.subjectFragile X Mental Retardation Protein
dc.subjectG-Quadruplexes
dc.titleFRAXE-associated mental retardation protein (FMR2) is an RNA-binding protein with high affinity for G-quartet RNA forming structure
dc.typeJournal article
pubs.publication-statusPublished

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