title: BC1-FMRP interaction is modulated by 2'-O-methylation: RNA-binding activity of the tudor domain and translational regulation at synapses.
abstract: The brain cytoplasmic RNA, BC1, is a small non-coding RNA that is found in different RNP particles, some of which are involved in translational control. One component of BC1-containing RNP complexes is the fragile X mental retardation protein (FMRP) that is implicated in translational repression. Peptide mapping and computational simulations show that the tudor domain of FMRP makes specific contacts to BC1 RNA. Endogenous BC1 RNA is 2'-O-methylated in nucleotides that contact the FMRP interface, and methylation can affect this interaction. In the cell body BC1 2'-O-methylations are present in both the nucleus and the cytoplasm, but they are virtually absent at synapses where the FMRP-BC1-mRNA complex exerts its function. These results strongly suggest that subcellular region-specific modifications of BC1 affect the binding to FMRP and the interaction with its mRNA targets. We finally show that BC1 RNA has an important role in translation of certain mRNAs associated to FMRP. All together these findings provide further insights into the translational regulation by the FMRP-BC1 complex at synapses.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, Faculty of Medicine, University of Rome Tor Vergata, Via Montpellier, 1. 00133, Rome, Italy.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lacoux
authors.forename: Daniele
authors.initials: D
authors.lastname: Di Marino
authors.forename: Pietro Pilo
authors.initials: PP
authors.lastname: Boyl
authors.forename: Francesca
authors.initials: F
authors.lastname: Zalfa
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ciotti
authors.forename: Mattia
authors.initials: M
authors.lastname: Falconi
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.forename: Tilmann
authors.initials: T
authors.lastname: Achsel
authors.forename: Annie
authors.initials: A
authors.lastname: Mougin
authors.forename: Michèle
authors.initials: M
authors.lastname: Caizergues-Ferrer
authors.forename: Claudia
authors.initials: C
authors.lastname: Bagni
mesh_terms: D000818:Animals; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008958:Models, Molecular; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020733:RNA, Small Cytoplasmic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; D020733:RNA, Small Cytoplasmic; C117734:BC1 RNA; C497684:Fmr1 protein, mouse