title: Identification of consensus binding sites clarifies FMRP binding determinants.
abstract: Fragile X mental retardation protein (FMRP) is a multifunctional RNA-binding protein with crucial roles in neuronal development and function. Efforts aimed at elucidating how FMRP target mRNAs are selected have produced divergent sets of target mRNA and putative FMRP-bound motifs, and a clear understanding of FMRP's binding determinants has been lacking. To clarify FMRP's binding to its target mRNAs, we produced a shared dataset of FMRP consensus binding sequences (FCBS), which were reproducibly identified in two published FMRP CLIP sequencing datasets. This comparative dataset revealed that of the various sequence and structural motifs that have been proposed to specify FMRP binding, the short sequence motifs TGGA and GAC were corroborated, and a novel TAY motif was identified. In addition, the distribution of the FCBS set demonstrates that FMRP preferentially binds to the coding region of its targets but also revealed binding along 3' UTRs in a subset of target mRNAs. Beyond probing these putative motifs, the FCBS dataset of reproducibly identified FMRP binding sites is a valuable tool for investigating FMRP targets and function.
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Bart R
authors.initials: BR
authors.lastname: Anderson
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Chopra
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Suhl
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA swarren@emory.edu.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Warren
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA gbassel@emory.edu.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Bassell
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D003062:Codon / Q000235:genetics; D016384:Consensus Sequence; D019175:DNA Methylation / Q000235:genetics; D030562:Databases, Protein; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000737:chemistry / Q000378:metabolism*; D054856:G-Quadruplexes; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D059372:Nucleotide Motifs / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D003062:Codon; D051860:Fragile X Messenger Ribonucleoprotein 1; D035683:MicroRNAs; D012333:RNA, Messenger