RNA polymerase: linear competitive inhibition by bis-(3' to 5')-cyclic dinucleotides,NpNp.

We have investigated the possible role of the bis-(3' to 5')-cyclic dinucleotides UpUp and ApUp as kinetic inhibitors of the DNA dependent RNA polymerase enzyme of E. coli, using T7 delta D111 deletion mutant DNA and several synthetic DNA polymers as templates. We have established that UpUp is a linear competitive inhibitor of the initiation phase of the polymerization (Ki = 28 microM using T7 delta D111 DNA as a template), but that it has no effect when added during the elongation phase. The compound ApUp is an inhibitor of the reaction only when poly(dA-T).poly(dA-T) is used as a template, and UpUp is an inhibitor of the reaction when poly(dA).poly(dT) was employed as the DNA template.