A series of t-PA cDNA mutants containing different parts of 3’-UTR sequences have beenconstructed.In vitro translation of t-PA transcripts in rabbit reticulocyte lysates and its expression in COS-7cells show that the 3’-UTR sequence has a very strong inhibitory effect on t-PA translation.The deletion of3’-UTR results in 3—8-fold increase of t-PA expression.Further study shows that an AU-rich sequence of some200 nt at 3’ end of 3’-UTR is responsible for the translational inhibition.RNA stability experiment reveals thatthe AU-rich segment leads to a 3-fold decrease of t-PA mRNA stability.The insertion of this segment into the3’-UTR of luciferase gene results in an obvious inhibition of Luc expression.A model is proposed for theregulation of t-PA expression.
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