摘要
RNA can catalyze and participate in many chemical and biochemical reactions. Non-coding RNAs （ncRNA） can regulate cellular transcription and translation reactions. We have demonstrated biochemically that RNA can also interfere with DNA polymerization via transforming DNA polymerase into deoxyribonucleoside triphosphate diphosphatase （dNTP-DPase）. RNA, even with six nucleotides, can transform DNA polymerase into dNTP-DPase, and the dNTP-DPase activity causes the hydrolysis of dNTPs into dNMPs and pyrophosphate. Moreover, we have found that DNA polymerases from several families generally have similar RNA-dependent dNTP-DPase activity. We have also observed that in the presence of RNA, when the dNTP concentrations are relatively low, and that the dNTP-DPase activity can deplete dNTPs and interfere with DNA polymerization Thus, we have discovered for the first time that in the presence of RNA, DNA polymerase can behave as a diphosphatase and inhibit DNA synthesis when dNTP quantity is low. These in vitro observations might imply a plausible role of RNA in vivo, such as suppressing DNA synthesis during a resting phase （Go） of the cell cycle, when RNA quantity is high and dNTP quantity is low.
RNA can catalyze and participate in many chemical and biochemical reactions.Non-coding RNAs(ncRNA)can regulate cellular transcription and translation reactions.We have demonstrated biochemically that RNA can also interfere with DNA polymerization via transforming DNA polymerase into deoxyribonucleoside triphosphate diphosphatase(dNTP-DPase).RNA,even with six nucleotides,can transform DNA polymerase into dNTP-DPase,and the dNTP-DPase activity causes the hydrolysis of dNTPs into dNMPs and pyrophosphate.Moreover,we have found that DNA polymerases from several families generally have similar RNA-dependent dNTP-DPase activity.We have also observed that in the presence of RNA,when the dNTP concentrations are relatively low,and that the dNTP-DPase activity can deplete dNTPs and interfere with DNA polymerization.Thus,we have discovered for the first time that in the presence of RNA,DNA polymerase can behave as a diphosphatase and inhibit DNA synthesis when dNTP quantity is low.These in vitro observations might imply a plausible role of RNA in vivo,such as suppressing DNA synthesis during a resting phase(G0)of the cell cycle,when RNA quantity is high and dNTP quantity is low.
基金
financially supported by the Georgia Cancer Coalition(GCC)Distinguished Cancer Clinicians and Scientists,USA NSF(IIP-1340153)and NIH(R01GM095881)
