Species-specific differential cleavage and polyadenylation of plasminogen activator inhibitor type 1 hnRNA.
Plasminogen activator inhibitor type 1 (PAI-1) is the primary physiologic inhibitor of the naturally occurring plasminogen activators. In higher 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 regulated in a tissue-specific fashion in humans. In other mammals only the 3.2 kb mRNA has been detected. The putative downstream polyadenylation 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 position that could generate the shorter mRNA species. To determine whether 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 acquired recently during primate evolution we prepared plasmids in which the 3' nontranslated region of the human PAI-1 gene or the mouse PAI-1 cDNA was inserted downstream of the neomycin gene in the plasmid pSV2neo. We show that the 3'-nontranslated region of the human PAI-1 gene but not the mouse PAI-1 cDNA conferred alternative cleavage and polyadenylation to the neomycin gene in transfected human Hep G2 cells as well as mouse NIH3T3 and rat L6 cells.
Fattal
P G
PG
Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110.
Billadello
J J
JJ
D017398:Alternative Splicing; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D051379:Mice; D009694:Nucleic Acid Precursors / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011061:Poly A / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012332:RNA, Heterogeneous Nuclear / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D013045:Species Specificity
D009694:Nucleic Acid Precursors; D017395:Plasminogen Activator Inhibitor 1; D012332:RNA, Heterogeneous Nuclear; D012333:RNA, Messenger; D011061:Poly A