title: Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG-repeat.
abstract: Fragile X syndrome is associated with massive expansion of a CGG trinucleotide repeat within the FMR-1 gene and transcriptional silencing of the gene due to abnormal methylation. Partial cDNA sequence of the human FMR-1 has been reported. We report here the isolation and characterization of cDNA clones encoding the murine homologue, fmr-1, which exhibit marked sequence identity with the human gene, including the conservation of the CGG repeat. A conserved ATG downstream of the CGG repeat in human and mouse and an in-frame stop codon in other human 5' cDNA sequences demarcate the FMR-1 coding region and confine the CGG repeat to the 5' untranslated region. We also present evidence for alternative splicing of the FMR-1 gene in mouse and human brain and show that one of these splicing events alters the FMR-1 reading frame, predicting isoforms with novel carboxy termini.
authors.affiliation: Howard Hughes Medical Institute, Emory University School of Medicine, Atlanta, Georgia 30322.
authors.forename: C T
authors.initials: CT
authors.lastname: Ashley
authors.forename: J S
authors.initials: JS
authors.lastname: Sutcliffe
authors.forename: C B
authors.initials: CB
authors.lastname: Kunst
authors.forename: H A
authors.initials: HA
authors.lastname: Leiner
authors.forename: E E
authors.initials: EE
authors.lastname: Eichler
authors.forename: D L
authors.initials: DL
authors.lastname: Nelson
authors.forename: S T
authors.initials: ST
authors.lastname: Warren
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D014176:Protein Biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
chemical_list: D009838:Oligodeoxyribonucleotides