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Human RNase A is secreted by pancreatic acinar cells and can be neutralized by the proteolytic enzyme, secretory leukocyte protease inhibitor. Here we show that RNase A does not undergo an alternative splicing in humans as previously reported in mice. To analyse whether the unique (H3-G6-G7-F8-R9-R10-G11) domain of RNase A influences its susceptibility to proteases, the wild-type RNase A and a RNase A mutant (in which the H3-G6-G7-F8-R9-R10-G11 domain is deleted; Leu41-Glu53 replaced by Gly) were studied. Following transient expression in COS cells and in hepatoma cells, the RNase A mutant was rapidly degraded. In contrast, the wild-type protein was fully protected against proteolysis in the plasma membrane. The results suggest that the H3-G6-G7-F8-R9-R10-G11 domain of RNase A is required for its protection against proteolysis and might, therefore, be involved in the intracellular sorting of RNase A, as proposed for RNase 2 (Chang, S. C., Rabinowitz, H. J., Rebers, O. H., Fleming, D. R. and Chmielecki, M. A. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 3942-3946).Jae C. Hong/Associated Press
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