RNA-dependent RNA polymerase

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RNA-dependent RNA polymerase (RdRP), or RNA replicase, is an enzyme that catalyzes the replication of RNA from an RNA template. This is in contrast to a typical RNA polymerase, which catalyzes the transcription of RNA from a DNA template.

Viral RdRPs were discovered in the early 1960s from studies on mengovirus and polio virus when it was observed that these viruses were not sensitive to actinomycin D, a drug that inhibits cellular DNA directed RNA synthesis.This lack of sensitivity suggested that there was a virus specific enzyme that could copy RNA from an RNA template and not from a DNA template.

The most famous example of RdRP is the polio virus. The virus is made up of RNA which enters the cell through receptor-mediated endocytosis. From there, the RNA is able to act as a template for complementary RNA synthesis, immediately. The complementary strand is then, itself, able to act as a template for the production of new viral genomes which are further packaged and released from the cell ready to infect more host cells. The advantage of this method of replication is that there is no DNA stage, replication is quick and easy. The disadvantage is that there is no 'back-up' DNA copy.

Many RdRPs are associated tightly with membranes and are therefore difficult to study. The best known RdRPs are polioviral 3Dpol, vesicular stomatitis virus L, and hepatitis C virus NS5b protein.

Many eukaryotes also have RdRPs involved in RNA interference; these amplify microRNAs and small temporal RNAs and produce double-stranded RNA using small interfering RNAs as primers.^[1], but in fact these same RdRPs that are used in the defense mechanisms can be kidnapped by RNA viruses for their benefit.