INHIBITORY EFFECT OF 3'-UNTRANSLATED REGION (3'-UTR) OF HUMAN TISSUE-PLASMINOGEN ACTIVATOR (HT-PA) MESSENGER-RNA ON ITS EXPRESSION

A series of t-PA cDNA mutants containing different parts of 3'-UTR seq uences have been constructed. In vitro translation of t-PA transcripts in rabbit reticulocyte lysates and its expression in COS-7 cells show that the 3'-UTR sequence has a very strong inhibitory effect on t-PA translation. The deletion of 3'-UTR results in 3-8-fold increase of t- PA expression. Further study shows that an AU-rich sequence of some 20 0 nt at 3' end of 3'-UTR is responsible for the translational inhibiti on. RNA stability experiment reveals that the AU-rich segment leads to a 3-fold decrease of t-PA mRNA stability. The insertion of this segme nt into the 3'-UTR of luciferase gene results in an obvious inhibition of Luc expression. A model is proposed for the regulation of t-PA exp ression.