THE CHICKEN FMR1 GENE IS HIGHLY CONSERVED WITH A CCT 5'-UNTRANSLATED REPEAT AND ENCODES AN RNA-BINDING PROTEIN

The transcriptional silencing of the human gene, fragile X mental reta rdation 1 (FMR1), is due to abnormal methylation in response to an exp anded 5'-untranslated CGG trinucleotide repeat and accounts for most c ases of fragile X syndrome, a frequent inherited form of mental retard ation. Although the encoded fragile X mental retardation protein (FMRP ) is known to have properties of a RNA-binding protein, the precise fu nction of FMRP remains to be elucidated. We report the cloning of the chicken homolog of FMR1 and show strong evolutionary conservation, wit h nucleotide and amino acid identities of 85 and 92%, respectively, be tween chicken and human. In place of the mammalian CGG; trinucleotide repeat, a 99-nt tripartite repetitive element containing a CCT trinucl eotide repeat banked on both sides by dinucleotide repeats was identif ied. Blocks of highly conserved 3'-untranslated sequence were also fou nd. Within the coding region, two copies each of the highly conserved It homology motif and the Arg-Gly-Gly (RGG) box motif, both ribonucleo tide particle family domains implicated in RNA binding, were identifie d. Chicken FMRP was found to bind RNA in vitro, and this activity corr elated with the presence of the carboxy-terminal portion of the protei n that includes the RGG motifs. (C) 1996 Academic Press, Inc.