Differential splicing of transcripts encoding the orphanin FQ/nociceptin precursor

Orphanin FQ or nociceptin (OFQ/N), the heptadecapeptide agonist for the NOP receptor, is derived by proteolytic processing from a precursor protein, preproOFQ/N. Previous studies have reported alternative splicing between exons 3 and 4 of the mouse OFQ/N transcript, which, upon translation, would yield precursor proteins with different C-termini. Using RT-PCR, we identified similar alternative splicing of preproOFQ/N transcripts in humans and rats. In addition, we identified two novel human preproOFQ/N splice variants from which exon 2 has been excised and which also undergo alternative splicing between exons 3 and 4. Exon 2 contains the translational start site for preproOFQ/N and encodes the signal peptide sequence. In vitro translation of cRNAs lacking exon 2 yields shorter translation products which arise from an alternative initiator methionine located within exon 3. The resulting proteins would lack a signal peptide sequence, which would likely alter their cellular trafficking and processing.