Annexin VII is believed to be required for proper Ca(2+)-homeostasis in Dictyostelium discoideum cells. As was previously reported, the expression of Annexin VII gene increased during the transition of D. discoideum Ax-2 cells from growth to differentiation. We have casually cloned an interesting gene, Quit3, by the differential plaque hybridization. Quit3 had no coding region, and was expressed more predominantly in the growth phase than in the differentiation phase. Unexpectedly, this gene was found to encode the complementary sequence of Annexin VII. Therefore, it is most likely that the Quit3 mRNA may regulate the Annexin VII synthesis by the natural antisense transcript via an antisense RNA-RNA interaction, thus resulting in striking increase of Annexin VII production in the phase-shift of cells from growth to differentiation. Since Annexin VII is known to be coded for by a single gene in Dictyostelium, the antisense RNA seemed to be encoded in the same genetic locus as the Annexin VII mRNA.