Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG-repeat.
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.
Ashley
C T
CT
Howard Hughes Medical Institute, Emory University School of Medicine, Atlanta, Georgia 30322.
Sutcliffe
J S
JS
Kunst
C B
CB
Leiner
H A
HA
Eichler
E E
EE
Nelson
D L
DL
Warren
S T
ST
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
D009838:Oligodeoxyribonucleotides