5-Fluorouracil inhibits dihydrofolate reductase precursor mRNA processing and/or nuclear mRNA stability in methotrexate-resistant KB cells - PubMed (original) (raw)
. 1989 Dec 15;264(35):21413-21.
Affiliations
- PMID: 2592384
Free article
5-Fluorouracil inhibits dihydrofolate reductase precursor mRNA processing and/or nuclear mRNA stability in methotrexate-resistant KB cells
C L Will et al. J Biol Chem. 1989.
Free article
Abstract
This laboratory previously reported that 5-fluorouracil (FUra) increases dihydrofolate reductase (DHFR) precursor mRNA (pre-mRNA) levels relative to DHFR mRNA levels in a methotrexate-resistant KB cell line; these data suggested that incorporation of FUra into RNA may, in part, lead to cell death through the inhibition of mRNA processing (Will, C. L., and Dolnick, B.J. (1987) J. Biol. Chem. 262, 5433-5436). Utilizing a methotrexate-resistant KB cell line designated 1BT, we now report the kinetic basis for altered levels of DHFR RNA observed in FUra-treated cells. Long-term exposure to FUra had no effect on the steady-state level of DHFR pre-mRNA containing intron V or I. However, steady-state levels of total DHFR mRNA decreased 2.0-fold on a per cell basis in cells exposed to 1.0 microM FUra. No significant change in the half-life of total DHFR mRNA or pre-mRNA was observed in cells exposed to FUra (t1/2 = approximately 11.5 h and 50 min, respectively). Nuclear/cytoplasmic RNA labeling experiments demonstrated that the rate of nuclear DHFR RNA conversion to cytoplasmic DHFR mRNA decreased approximately 1.8-fold in FUra-treated cells. These results provide further evidence the FUra may inhibit processing of mRNA precursors and/or affect the stability of nuclear DHFR mRNA.
Similar articles
- Acute effect of 5-fluorouracil on cytoplasmic and nuclear dihydrofolate reductase messenger RNA metabolism.
Armstrong RD, Lewis M, Stern SG, Cadman EC. Armstrong RD, et al. J Biol Chem. 1986 Jun 5;261(16):7366-71. J Biol Chem. 1986. PMID: 2423519 - Molecular mechanisms of resistance to antifolates, a review.
Banerjee D, Ercikan-Abali E, Waltham M, Schnieders B, Hochhauser D, Li WW, Fan J, Gorlick R, Goker E, Bertino JR. Banerjee D, et al. Acta Biochim Pol. 1995;42(4):457-64. Acta Biochim Pol. 1995. PMID: 8852336 Review. - Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase.
Banerjee D, Mayer-Kuckuk P, Capiaux G, Budak-Alpdogan T, Gorlick R, Bertino JR. Banerjee D, et al. Biochim Biophys Acta. 2002 Jul 18;1587(2-3):164-73. doi: 10.1016/s0925-4439(02)00079-0. Biochim Biophys Acta. 2002. PMID: 12084458 Review.
Cited by
- Incorporation of 5-fluorouracil into U2 snRNA blocks pseudouridylation and pre-mRNA splicing in vivo.
Zhao X, Yu YT. Zhao X, et al. Nucleic Acids Res. 2007;35(2):550-8. doi: 10.1093/nar/gkl1084. Epub 2006 Dec 14. Nucleic Acids Res. 2007. PMID: 17169984 Free PMC article. - Knock-down of 25 kDa subunit of cleavage factor Im in Hela cells alters alternative polyadenylation within 3'-UTRs.
Kubo T, Wada T, Yamaguchi Y, Shimizu A, Handa H. Kubo T, et al. Nucleic Acids Res. 2006;34(21):6264-71. doi: 10.1093/nar/gkl794. Epub 2006 Nov 10. Nucleic Acids Res. 2006. PMID: 17098938 Free PMC article. - 5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development.
Grem JL. Grem JL. Invest New Drugs. 2000 Nov;18(4):299-313. doi: 10.1023/a:1006416410198. Invest New Drugs. 2000. PMID: 11081567 Review. - Tissue-specific promoters of the alpha human folate receptor gene yield transcripts with divergent 5' leader sequences and different translational efficiencies.
Roberts SJ, Chung KN, Nachmanoff K, Elwood PC. Roberts SJ, et al. Biochem J. 1997 Sep 1;326 ( Pt 2)(Pt 2):439-47. doi: 10.1042/bj3260439. Biochem J. 1997. PMID: 9291116 Free PMC article. - Cloning and characterization of a naturally occurring antisense RNA to human thymidylate synthase mRNA.
Dolnick BJ. Dolnick BJ. Nucleic Acids Res. 1993 Apr 25;21(8):1747-52. doi: 10.1093/nar/21.8.1747. Nucleic Acids Res. 1993. PMID: 8493092 Free PMC article.