Cotranscription and intergenic splicing of human P2Y(11) SSF1 genes

The P2Y(11) receptor is an ATP receptor positively coupled to the cAMP and phosphoinositide pathways. Ssf1 is a Saccharomyces cerevisiae nuclear prote in, which plays an important role in mating. The gene encoding the human or thologue of SSF1 is adjacent to the P2Y(11) gene on chromosome 19. During t he screening of placenta cDNA libraries, we isolated a chimeric clone resul ting from the intergenic splicing between the P2Y(11) and SSF1 genes. The f usion protein was stably expressed in CHO-K1 cells where it generated a cAM P response to ATP qualitatively indistinguishable from that of the P2Y(11) receptor. According to both Western blotting and cAMP response, the express ion of the fusion protein in the transfected cells was clearly lower than t hat of the P2Y(11) receptor. Both P2Y(11) and SSF1 probes detected a 5.6-kb messenger RNA with a similar pattern of intensity in each of 11 human tiss ues. The ubiquitous presence of chimeric transcripts and their up-regulatio n during granulocytic differentiation indicate that the transgenic splicing between the P2Y(11) and the SSF1 genes is a common and regulated phenomeno n, There are very few examples of intergenic splicing in mammalian cells, a nd this is the first case involving a G-protein-coupled receptor.