Sequence specific binding of cytosolic proteins to a 12 nucleotide sequence in the 5' untranslated region of FMR1 mRNA.
The 5' untranslated region of human FMR1 mRNA is highly conserved, including a 26 nucleotide sequence containing a tandem 12 nucleotide repeat of (G/C)CU(C/G)CCGG(G/A)G(G/C)(G/C) which predates the evolutionary divergence between birds and mammals. We show here that this 12 nucleotide sequence in FMR1 mRNA is a specific binding site for small (< 20 kDa) cytosolic proteins of rat brain. Point mutation analysis identified two guanine residues in this 12 nucleotide repeat which are essential for protein binding. The 12 nucleotide motif sequence was found in the 5'UTR of at least 15 other genes and could be a common target site for these cytosolic RNA-binding proteins.
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Howard Hughes Medical Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000378:metabolism; D002457:Cell Extracts / Q000737:chemistry; D016384:Consensus Sequence / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D003593:Cytoplasm / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D051860:Fragile X Messenger Ribonucleoprotein 1; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D017354:Point Mutation / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012260:Ribonucleases / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
D002457:Cell Extracts; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012260:Ribonucleases; C497685:Fmr1 protein, rat