| First Author | Ke Y | Year | 1996 |
| Journal | Mol Cell Biol | Volume | 16 |
| Issue | 1 | Pages | 376-83 |
| PubMed ID | 8524318 | Mgi Jnum | J:31082 |
| Mgi Id | MGI:78551 | Doi | 10.1128/mcb.16.1.376 |
| Citation | Ke Y, et al. (1996) Splicing signals are required for S-phase regulation of the mouse thymidylate synthase gene. Mol Cell Biol 16(1):376-83 |
| abstractText | The thymidylate synthase (TS) gene is expressed at a much higher level in cells undergoing DNA replication than in nondividing cells. In growth-stimulated mammalian cells, TS mRNA content increases 10 to 20-fold as cells progress from G1 through S phase. However, the rate of transcription of the TS gene does not increase during this interval, indicating that the gene is regulated at the posttranscriptional level. We have shown that both the promoter of the mouse TS gene and TS introns are necessary (although neither is sufficient) for S-phase-specific regulation of TS mRNA content. In the present study, we examined in more detail the role of introns in regulating TS mRNA levels in growth-stimulated cells. TS minigenes that contain normal or modified introns were stably transfected into mouse 3T6 fibroblasts, and the regulation of the minigenes was compared with that of the endogenous TS gene. TS minigenes that contain TS intron 1 or 2 maintain S-phase regulation. Deletion of most of the interior of the introns had only minor effects on regulation. However, when splicing of the intron was inhibited by alteration of the splice donor and acceptor sites, the minigene was expressed at a constant level following growth stimulation. Minigenes consisting of the TS promoter linked to either a luciferase or a human beta-globin indicator gene were growth regulated when spliceable introns were included in the minigenes. However, when the introns were eliminated, the minigenes were expressed at a constant level.(ABSTRACT TRUNCATED AT 250 WORDS) |
