Inhibitory effect of 3'-untranslated region (3'-UTR) of human tissue-plasminogen activator (ht-PA) mRNA on its expression.
A series of t-PA cDNA mutants containing different parts of 3'-UTR sequences 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 200 nt at 3' end of 3'-UTR is responsible for the translational inhibition. RNA stability experiment reveals that the AU-rich segment leads to a 3-fold decrease of t-PA mRNA stability. The insertion of this segment 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 expression.
Ouyang
Y
Y
Molecular Genetics Center, Institute of Biotechnology, Beijing, China.
Huang
P
P
Huang
C
C
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D012156:Reticulocytes / Q000166:cytology / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000235:genetics* / Q000378:metabolism
D018076:DNA, Complementary; D012333:RNA, Messenger; D010959:Tissue Plasminogen Activator