Cell-free biosynthesis of somatostatin precursors: Evidence for multiple forms of preprosomatostatin

It has been demonstrated [Shields, D. (1980) J. Biol. Chem. 255, 11625-11628] that mRNA isolated from the islets of Langerhans codes for two preposomatostatin molecules of apparent molecular weights 18,000 and 19,000, respectively. Here evidence is presented that in vitro translation of pancreatic islet mRNA in two different cell-free protein-synthesizing systems directs the synthesis of up to nine distinct forms of somatostatin-immunoreactive polypeptides. The multiplicity of the preprosomatostatin molecules was the result of initiation of translation from separate species of mRNA as demonstrated by amino-terminal labeling with N-formyl-[35S]Met-tRNAMetf. Translation of islet mRNA isolated from different individual animals showed that all of the preposomatostatin polypeptides were present amongst the cell-free products, which implies that the multiple forms were not due to genetic variation in the wild population. Based on their apparent molecular weights and distinctly different isoelectric points, the different preprosomatostatin molecules could be classified into two major families. These results suggest that the anglerfish preprosomatostatins are encoded by separate mRNA species and are consistent with the existence of a multigene family for somatostatin.