PT  - JOURNAL ARTICLE
AU  - FRED H. REYNOLDS, JR.
AU  - PAULA M. PITHA
AU  - RONALD CHUANG
AU  - TU-CHEN CHENG
AU  - HAIG H. KAZAZIAN, JR.
AU  - DEZIDER GRUNBERGER
TI  - Effects of Poly(9-vinyladenine) and Poly(1-vinyluracil) on Messenger Ribonucleic Acid Template Activity
DP  - 1975 Nov 01
TA  - Molecular Pharmacology
PG  - 708--715
VI  - 11
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/11/6/708.short
4100  - http://molpharm.aspetjournals.org/content/11/6/708.full
SO  - Mol Pharmacol1975 Nov 01; 11
AB  - The neutral polynucleotide analogues poly(9-vinyladenine) and poly(1-vinyluracil) were found to inhibit [3H]dTTP incorporation in a system containing rabbit hemoglobin mRNA as template, oligo(dT) as primer, and purified avian myeloblastosis RNA-dependent DNA polymerase. The incorporation was inhibited 50% at an analogue concentration of 0.1 mM in base residues. Complexes of homopolynucleotides with vinyl polymers were tested as templates in a cell-free amino acid-incorporating system prepared from Krebs II ascites cells. Poly(9-vinyladenine) inhibited poly(U)-stimulated [14C]phenylalanine incorporation, while poly(1-vinyluracil) inhibited poly(A)-stimulated [14c]lysine incorporation. In neither case was the noncomplementary vinyl polymer inhibitory. Although poly(9-vinyladenine) had no effect on rabbit globin mRNA-stimulated amino acid incorporation in a cell-free system prepared from the Krebs II ascites tumor, poly(1-vinyluracil) was slightly inhibitory, with 50% inhibition occurring at a concentration of 10 mM uracil residues. However, similar inhibition occurred with a preparation of mRNA which did not contain the 3'-terminal poly(A) sequence, indicating that the inhibition occurring with high concentrations of poly(1-vinyluracil) does not involve the 3'-teminal poly(A) of the mRNA. The radioactive proteins produced in the cell-free system both with and without vinyl polymer coelectrophoresed with rabbit globin marker. These results suggest that the 3'-terminal poly(A) sequence of mRNA does not function in cell-free protein synthesis. Furthermore, the failure of the vinyl polymers to significantly inhibit cell-free protein synthesis suggests that the mechanism of vinyl polymer inhibition of murine leukemia virus replication in mouse cells involves inhibition of RNA-dependent DNA polymerase rather than inhibition of viral protein synthesis. ACKNOWLEDGMENT We thank Dr. Josef Pitha for his gift of vinyl polymers and for numerous helpful discussions on the properties of vinyl polymers and their behavior in biological systems.