DIFFERENTIAL IN-VITRO TRANSLATION OF THE PRECURSORS OF BOVINE PANCREATIC TRYPSIN-INHIBITOR AND ITS ISOINHIBITOR-II IS CONTROLLED BY THE 5'-END REGION OF THEIR MESSENGER-RNAS

Bovine spleen inhibitor (SI II), a 58-amino-acid protein present in se veral bovine tissues, is an isoinhibitor of bovine pancreatic trypsin inhibitor (BPTI or aprotinin). These two proteins, which differ in sev en amino-acidic residues, have very similar inhibitory activity agains t serine proteinases and are biosynthesized as two separate precursors of 100 residues. Higher levels of BPTI, compared to SI II, are found in bovine lung, as well as in other bovine tissues, in contrast to the level in vivo of the corresponding mRNAs. SI mRNA possesses a 90-nt 5 '-end region, absent in BPTI mRNA, with an additional 5' AUG in a diff erent open reading frame (ORF). We have used an in vitro transcription /translation system to determine the effect of this upstream region on the efficiency of SI precursor translation. Full-length SI mRNA is tr anslated in vitro 6-fold less efficiently than BPTI mRNA. However, whe n SI mRNA lacks the 5' non-coding region, the translational efficiency of the 'truncated' transcript is significantly increased, reaching th e same level as that of BPTI mRNA. In all cases the 10500 Da precursor is the product of the in vitro translation. Our results indicate that the dramatic differences in translational efficiency of the mRNAs enc oding BPTI and SI II in vitro parallel the different levels of the two proteins in vivo, and could be attributed to the features of the 5' n on-coding region of SI mRNA.