Inhibition of ornithine decarboxylase and S-adenosylmethionine decarboxylase synthesis by antisense oligodeoxynucleotides |
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Authors: | Rentala Madhubala Anthony E Pegg |
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Institution: | (1) Departments of Cellular and Molecular Physiology and of Pharmacology, Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Centre, P. O. Box 850, 17033 Hershey, PA, USA;(2) School of Life Sciences, Jawaharlal Nehru University, 110 067 New Delhi, India |
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Abstract: | Oligodeoxynucleotides 18 nucleotides in length having sequences complementary to regions spanning the initiation codon regions of ornithine decarboyxlase or S-adenosylmethionine decarboxylase mRNAs were tested for their ability to inhibit translation of these mRNAs. In reticulocyte lysates, a strong and dose dependent reduction of ornithine decarboyxlase synthesis in response to mRNA from D-R L1210 cells was brought about by 5-AAAGCT GCTCATGGTTCT-3 which is complementary to the sequence from - 6 to + 12 of the mRNA sequence but there was no inhibition by 5-TGCAGCTTCCATCACCGT-3. Conversely, the latter oligodeoxynucleotide which is complementary to the sequence from – 6 to + 12 of the mRNA of S-adenosyl methionine decarboxylase was a strong inhibitor of the synthesis of this enzyme in response to rat prostate mRNA and the antisense sequence from ornithine decarboxylase had no effect. The translation of ornithine decarboxylase mRNA in a wheat germ system was inhibited by the antisense oligodeoxynucleotide at much lower concentration than those needed in the reticulocyte lysate suggesting that degradation of the hybrid by ribonuclease H may be an important factor in this inhibition. These results indicate that such oligonucleotides may be useful to regulate cellular polyamine levels and as probes to study control of mRNA translation.Abbreviations ODC
ornithine decarboxylase
- AdoMetDC
S-adenosylmethionine decarboxylase
- DFMO
difluoromethylornithine |
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Keywords: | polyamines ornithine decarboxylase S-adenosylmethionine decarboxylase antisense oligodeoxynucleotides |
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