The rat androgen-binding protein (ABP/SHBG) gene contains triplet repeats similar to unstable triplets: evidence that the ABP/SHBG and the fragile X-related 2 genes overlap.
The rat androgen-binding protein/sex hormone-binding globulin (ABP/SHBG) gene is regulated by promoters P1 and PA. P1 regulates the mRNA encoding secreted ABP/SHBG, whereas PA regulates an alternate mRNA which encodes a modified protein that is targeted to the nucleus. Promoter PA is GC rich, consisting of 70-80% GC residues. During routine BLAST sequence analysis it was discovered that this GC-rich region is highly related to the human fragile X-related protein 2 (FXR-2) 5'-untranslated RNA sequence. Furthermore, the nucleotide coding sequence of the initial 14 FXR-2 amino acid residues was identical in the ABP/SHBG gene. The 5'-untranslated FXR-2 sequence contains triplet (CGG) repeats, which are also present in the rat ABP/SHBG gene. The meiotic instability of CGG repeats in the human fragile X (FMR1) gene causes the fragile X mental retardation syndrome. The data presented here suggest that the ABP/SHBG and FXR-2 genes overlap with each gene transcribed in the opposite direction. In support of this structure, the human ABP/SHBG and the FXR-2 genes map to the same site on chromosome 17. Thus, the ABP/SHBG gene contains triplet repeats in the alternate promoter PA. It will be of particular interest to determine if triplet instability affects ABP/SHBG gene expression. A triplet instability in the X-linked androgen receptor gene causes spinal and bulbar muscular atrophy.
Joseph
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DR
Applied Genetics Laboratories, Biotechnology Development Institute, University of Florida, Alachua 32615, USA.
D000727:Androgen-Binding Protein / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D005600:Fragile X Syndrome / Q000235:genetics*; D005807:Genes, Overlapping; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics*; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D012738:Sex Hormone-Binding Globulin / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion; D018911:Trinucleotide Repeats
D000727:Androgen-Binding Protein; C096915:FXR2 protein, human; D016601:RNA-Binding Proteins; D012738:Sex Hormone-Binding Globulin