A SINE that acquired a role in signal transduction during evolution

We have discovered a new SINE that appears to have acquired a novel role in signal transduction in the lineage of a group of artiodactyls. SINEs are a group of retroposons which have been amplified and integrated into genomes by retroposition (Okada and Ohshima 1995) The majority of SINEs are believed to be parasitic and to represent junk DNA in host organisms. However, in certain cases, SINEs appear to have gained novel functions and to have become involved in biological processes. More than 10 such examples have been recorded, in which sequences of SINEs have become promoters that modify the expression of preexisting functional genes or provide a new polyadenylation signal (Britten 1996; Makalowski 1995). In other cases, SINEs have been integrated into the coding region and are translated into peptides, with resulting generation of protein variability. In fact, more than 30 SINEs have been found in the coding regions of mRNAs (Makalowski 1995). However, no examples of such messages playing an explicit role in an important biological process have yet been reported (Makalowski 1995). We recently characterized the CHR-1 SINEs, which are distributed exclusively among whales, cows, and hippopotamuses (Shimamura et al. 1997). In a BLASTN search (Altschul et al. 1990), we found an example of a CHR-1 SINE that was inserted into the coding region of mRNA for the EP3 subtype of receptor for bovine prostaglandin (PG) E2. It appears that this message with an integrated SINE plays a key role in the signal transduction that is mediated by the bovine EP3 receptor for PGE2. Prostaglandin E2 has a broad range of biological effects in diverse tissues that are mediated through its binding to specific receptors on plasma membranes. Four subtypes of receptors (EP1, EP2, EP3, and EP4) for PGE2 have been recognized on the basis of their respective responses to agonists and antagonists (Coleman et al. 1989). It has been proposed that the EP3 receptor mediates various very different effects of PGE2, such as inhibition of neurotransmitter release (Ohia and Jumblatt 1990), contraction of the uterus (Krall et al. 1984), inhibition of the reabsorption of sodium ions and water in kidney tubules (Nakao et al. 1989), and stimulation of catecholamine release from adrenal chromaffin cells (Tanaka et al. 1990). The EP3 receptor is a protein with seven transmembrane domains. The bovine EP3 receptor exists as