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Publication : Introns are essential for growth-regulated expression of the mouse thymidylate synthase gene.

First Author  Ash J Year  1993
Journal  Mol Cell Biol Volume  13
Issue  3 Pages  1565-71
PubMed ID  8095091 Mgi Jnum  J:3970
Mgi Id  MGI:52475 Doi  10.1128/mcb.13.3.1565
Citation  Ash J, et al. (1993) Introns are essential for growth-regulated expression of the mouse thymidylate synthase gene. Mol Cell Biol 13(3):1565-71
abstractText  The thymidylate synthase (TS) gene is expressed at much higher levels in proliferating cells than in quiescent cells. We have been studying the sequences that are important for regulating the mouse TS gene. We previously showed that DNA sequences upstream of the essential promoter elements as well as downstream of the ATG codon are both necessary (but neither is sufficient) for normal regulation in growth-stimulated cells. In the present study, we examined the possible roles of the coding region, polyadenylation signal, and introns as downstream regulatory elements. Minigenes consisting of 1 kb of the TS 5'-flanking region, the coding region (with or without various introns at their normal locations), and polyadenylation signals from the TS gene, the human beta-globin gene, and the bovine growth hormone gene were stably transfected into wild-type mouse 3T6 cells. Minigenes that contained introns 5 and 6, 1 and 2, or 1 alone were regulated regardless of which polyadenylation signal was included. A minigene that contained an internally deleted version of intron 1 was also regulated in response to growth stimulation. However, when all introns were omitted, there was little if any change in the level of minigene expression as cells progressed from G1 through S phase. These observations indicate that TS introns contain sequences that are necessary for normal growth-regulated expression of the mouse TS gene. These sequences appear to be associated with sequences that are important for splicing and to function in cooperation with upstream regulatory elements to bring about normal S-phase-specific expression.
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4 Authors

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