Renin is synthesized as a 50 000 dalton single‐chain polypeptide in cell‐free translation systems

A number of eukaryotic secretory proteins are synthesized as molecules with an amino-terminal extension of 16-25, mainly hydrophobic, amino acid residues, when their mRNAs are translated in cell-free systems devoid of microsomal membranes (reviewed [ 1,2]). This short extension is named the ‘pre-’ or ‘signal’ peptide and is thought to be essential for the secretion of these proteins [3]. In addition, many secretory proteins, such as some enzymes and peptide hormones, are derived by cleavage of large precursor chains (proenzymes or -hormones). Thus, in these latter cases, the initial translation products are single-chain pre-proenzymes or pre-prohormones [12,4,51. We have isolated total poly(A)-containing mRNA from renin-rich submaxillary glands of mice. These mRNAs were translated, in the presence of [35S] methionine, in two mRNA-dependent cell-free systems from wheat germ and reticulocyte lysate, respectively. The radioactive translation products were subjected to immunoprecipitation with antirenin or pure renin-specific Fab fragments, and characterized by SDS-acrylamide gel electrophoresis. Our data indicate that renin is initially synthesized as a precursor -10 000 daltons larger than the enzymatically active 40 000 dalton renin. In analogy with other enzyme precursors, this may well represent a pre-prorenin.