title: On BC1 RNA and the fragile X mental retardation protein.
abstract: The fragile X mental retardation protein (FMRP), the functional absence of which causes fragile X syndrome, is an RNA-binding protein that has been implicated in the regulation of local protein synthesis at the synapse. The mechanism of FMRP's interaction with its target mRNAs, however, has remained controversial. In one model, it has been proposed that BC1 RNA, a small non-protein-coding RNA that localizes to synaptodendritic domains, operates as a requisite adaptor by specifically binding to both FMRP and, via direct base-pairing, to FMRP target mRNAs. Other models posit that FMRP interacts with its target mRNAs directly, i.e., in a BC1-independent manner. Here five laboratories independently set out to test the BC1-FMRP model. We report that specific BC1-FMRP interactions could be documented neither in vitro nor in vivo. Interactions between BC1 RNA and FMRP target mRNAs were determined to be of a nonspecific nature. Significantly, the association of FMRP with bona fide target mRNAs was independent of the presence of BC1 RNA in vivo. The combined experimental evidence is discordant with a proposed scenario in which BC1 RNA acts as a bridge between FMRP and its target mRNAs and rather supports a model in which BC1 RNA and FMRP are translational repressors that operate independently.
authors.affiliation: The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Iacoangeli
authors.forename: Timofey S
authors.initials: TS
authors.lastname: Rozhdestvensky
authors.forename: Natalia
authors.initials: N
authors.lastname: Dolzhanskaya
authors.forename: Barthélémy
authors.initials: B
authors.lastname: Tournier
authors.forename: Janin
authors.initials: J
authors.lastname: Schütt
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brosius
authors.forename: Robert B
authors.initials: RB
authors.lastname: Denman
authors.forename: Edouard W
authors.initials: EW
authors.lastname: Khandjian
authors.forename: Stefan
authors.initials: S
authors.lastname: Kindler
authors.forename: Henri
authors.initials: H
authors.lastname: Tiedge
mesh_terms: D000818:Animals; D019921:Biotinylation; D001921:Brain / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005786:Gene Expression Regulation; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D009693:Nucleic Acid Hybridization; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D020733:RNA, Small Cytoplasmic; D016601:RNA-Binding Proteins / Q000737:chemistry
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; D020733:RNA, Small Cytoplasmic; D016601:RNA-Binding Proteins; C117734:BC1 RNA