title: FRAXE-associated mental retardation protein (FMR2) is an RNA-binding protein with high affinity for G-quartet RNA forming structure.
abstract: FRAXE 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.
authors.affiliation: CNRS UMR 6097-Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
authors.forename: Mounia
authors.initials: M
authors.lastname: Bensaid
authors.forename: Mireille
authors.initials: M
authors.lastname: Melko
authors.forename: Elias G
authors.initials: EG
authors.lastname: Bechara
authors.forename: Laetitia
authors.initials: L
authors.lastname: Davidovic
authors.forename: Antonio
authors.initials: A
authors.lastname: Berretta
authors.forename: Maria Vincenza
authors.initials: MV
authors.lastname: Catania
authors.forename: Jozef
authors.initials: J
authors.lastname: Gecz
authors.forename: Enzo
authors.initials: E
authors.lastname: Lalli
authors.forename: Barbara
authors.initials: B
authors.lastname: Bardoni
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D022003:Cell Nucleus Structures / Q000737:chemistry; D002478:Cells, Cultured; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D054856:G-Quadruplexes; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009687:Nuclear Proteins; D012313:RNA; D016601:RNA-Binding Proteins; C512744:Aff2 protein, mouse