Thursday, November 29, 2012

The fidelity of RNA virus polymerases

  RNA viruses may have a proofreading function in their RNA dependent RNA polymerases. The proofreading function exchanges an incorrectly incorporated nucleotide into the correct one. This function was detected in influenza virus polymerase by cell free transcription system for example. Influenza virus polymerase makes GTP residues after the first nucleotide after the primer for initiation of transcription in the presence of the high concentrations of GTP. This GTP incorporated position should be actually set for CTP. However, the second nucleotide was removed by viral polymerase, and exchanged into CTP when the optimal amount of CTP exists. This experiment suggests the presence of a proofreading function in influenza virus polymerase.
 I want to demonstrate whether other RNA viruses have same function in their RNA synthesis machinery. It is very important to understand the fidelity of RNA virus polymerases. RNA viruses are known as highly mutation-prone pathogens in their genome, indicating that many mutated novel viruses appear due to the error-prone mechanism. If a virus has a proofreading function, why does it cause many mutations in their genome?

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