RNA-dependent RNA polymerase

RNA-dependent RNA polymerase
RNA Replicase structure.png
RNA Replicase structure 3PHU​.[1]
Identifiers
2.7.7.48
9026-28-2
Databases
IntEnz view
BRENDA entry
NiceZyme view
KEGG entry
metabolic pathway
profile
PDBsum
QuickGO
RNA dependent RNA polymerase
Identifiers
SymbolRdRP_1
PF00680
CL0027
IPR001205
2jlg
2jlg
RNA-directed RNA polymerase, flaviviral
Identifiers
SymbolRNA_pol_flaviviral
PF00972
IPR000208

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

RNA-dependent RNA polymerase (RdRp) is an essential protein encoded in the genomes of all RNA-containing viruses with no DNA stage i.e. only RNA viruses.[2][3] It catalyses synthesis of the RNA strand complementary to a given RNA template. The RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo), or a primer-dependent mechanism that utilizes a viral protein genome-linked (VPg) primer. The de novo initiation consists in the addition of a nucleoside triphosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product.[4][5]

History

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 is 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 that of the polio virus. The viral genome is composed 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 that 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.[6] In fact these same RdRPs that are used in the defense mechanisms can be usurped by RNA viruses for their benefit.[citation needed]

RdRps are highly conserved throughout viruses and is even related to telomerase, though the reason for such high conservation in such diverse organisms is an ongoing question as of 2009.[7] The similarity has led to speculation that viral RdRps are ancestral to human telomerase.