SPECIES-SPECIFIC DIFFERENTIAL CLEAVAGE AND POLYADENYLATION OF PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 HNRNA (VOL 21, PG 1463, 1993)

Plasminogen activator inhibitor type 1 (PAI-1) is the primary physiolo gic inhibitor of the naturally occurring plasminogen activators. In hi gher primates two forms of mature PAI-1 mRNA (3.2 kb and 2.2 kb) arise by alternative cleavage and polyadenylation of PAI-1 hnRNA which is r egulated in a tissue-specific fashion in humans. In other mammals only the 3.2 kb mRNA has been detected. The putative downstream polyadenyl ation site in humans that gives rise to the 3.2 kb PAI-1 mRNA consists of three overlapping copies of the consensus polyadenylation sequence while no consensus polyadenylation sequence is found upstream at a po sition that could generate the shorter mRNA species. To determine whet her differential cleavage and polyadenylation of PAI-1 mRNA is due to species-specific differences in trans-acting factors that process PAI- 1 mRNA or to the presence of a nonconsensus polyadenylation site acqui red recently during primate evolution we prepared plasmids in which th e 3' nontranslated region of the human PAI-1 gene or the mouse PAI-1 c DNA was inserted downstream of the neomycin resistance gene in the pla smid PSV2neo. We show that the 3'-nontranslated region of the human PA I-1 gene but not the mouse PAI-1 cDNA conferred alternative cleavage a nd polyadenylation to the neomycin gene in transfected human Hep G2 ce lls as well as mouse NIH3T3 and rat L6 cells.