Alternate splicing of human thromboxane synthase mRNA.
Two species of human thromboxane synthase (TXS) cDNA, called TXS-I and -II, were previously isolated (K. Ohashi, K.-H. Ruan, R. J. Kulmacz, K. K. Wu, and L.-H. Wang, 1992, J. Biol. Chem. 267, 789-793). TXS-II differs from TXS-I by a 163-bp deletion near the 3'-end of the coding region. Both types of TXS mRNA have now been demonstrated to be present in various blood and lung cultured cells. Analysis of the exon-intron boundaries of TXS genomic DNA revealed that the two mRNAs are generated via alternate splicing: TXS-II is produced by skipping an entire 163-bp exon which encodes the polypeptide segment containing the heme-binding cysteine conserved among other P450s. The mechanism by which alternate splicing occurs is probably due to the presence of a more powerful potential as the 3' acceptor site in the intron following the 163-bp exon. When expressed in baculovirus system, recombinant TXS-I catalyzed the formation of thromboxane A2 and 12-hydroxyheptadecatrienoic acid (HHT), whereas recombinant TXS-II did not synthesize thromboxane A2 or HHT. Alternate splicing of TXS RNA transcript thus may provide a mechanism for limiting cellular biosynthesis of thromboxane A2.
Wang
L H
LH
Division of Hematology, University of Texas Health Science Center at Houston 77030.
Tazawa
R
R
Lang
A Q
AQ
Wu
K K
KK
D017398:Alternative Splicing; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D008970:Molecular Weight; D012333:RNA, Messenger / Q000235:genetics; D013930:Thromboxane-A Synthase / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D012333:RNA, Messenger; D013930:Thromboxane-A Synthase