Intron 17 of the human retinoblastoma susceptibility gene encodes an actively transcribed G protein-coupled receptor gene.

Abstract

The human retinoblastoma susceptibility gene, a member of the tumor suppressor gene family, is located on chromosome 13q14.12-13q14.2 and consists of 27 exons that are distributed over 180 kb. This study shows that intron 17, the largest in size, consisting of nearly 72,000 bp, contains an open reading frame encoding a novel G protein-coupled receptor in the reverse orientation relative to the transcription of the retinoblastoma susceptibility gene. Correction of a frameshift mutation revealed that this novel G protein-coupled receptor is the human homolog of a chicken T-cell-specific receptor cDNA. This is an additional description of an actively transcribed protein-encoding gene positioned within an intron of another gene, suggesting that introns can have important structural functions.A common feature of eukaryotic genes is the presence of intervening sequences or introns, which must be excised from each RNA transcript to convert the precursor to an mRNA molecule that can code for the synthesis of a continuous protein.Introns range in size from <100 to >10,000 nucleotides and differ significantly from coding regions in exons, in that most of the nucleotide sequence of an intron can be altered without greatly affecting gene function. In addition, introns seem to have accumulated repetitive sequences and mutations rapidly during evolution, leading to the suggestion that they have no function at all and are largely genetic "junk." An exception to the view that introns do not encode functionally important sequences occurs in several genes specifying proteins involved in RNA processing and translation. Such genes often encode in their introns small nucleolar RNAs (snoRNAs), suggesting that cotranscription of snoRNAs with mRNAs for ribosomal or nucleolar proteins may provide a regulatory mechanism to coordinate accumulation of the different components required for ribosome biogenesis (Kiss et al. 1995;Tycowski et al. 1996). Although the majority of eukaryotic genes contain introns, to date such sequences have not been found to add to the level of genetic complexity by containing other protein-encoding genes. Only a few genes are known that contain additional open reading frames (ORFs) in their introns, such as the neurofibromatosis type 1 gene (Cawthorn et al. 1990;O'Connell et al. 1990;Viskochil et al. 1991). We show here that an actively transcribed gene encoding a T-cell specific, G protein-coupled receptor is located within intron 17 of the human retinoblastoma (RB) susceptibility gene.The human RB gene is located on chromosome 13q14.12-13q14.2 and consists of 27 exons that are distributed over 180 kb (Toguchida et al. 1993). The gene belongs to a family of tumor suppressor genes, and defects in this locus are responsible for retinoblastoma, a malignant tumor arising in the eyes of young children. Normally a 4.7-kb mRNA transcript is produced that encodes a 928 amino acid nuclear phosphoprotein. Of the 26 introns, intron 17 is the largest in size, consisting of nearly 72,000 bp.In the process of using PCR with ...

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