RNA-dependent RNA polymerase

RNA-dependent RNA polymerase (RdRp) plays a role in RNA replication and transcription. It catalyzes the synthesis of the RNA strand complementary to a given RNA template. RdRp is an essential protein encoded in the genomes of most RNA-containing viruses lacking a DNA stage.

Viral RdRp are extremely diverse but share common motifs that allow comparison. Some eukaryotes also contain RdRps involved in RNA interference that are structurally distinct from viral RdRps. RNA viruses are classified according to their RdRp homology.

Naming: By convention viral polymerases are called RNA/DNA-dependent whereas cellular polymerases are called RNA/DNA-directed.

Priming:

• Primer independent (Kitrinoviricota, Lernaviricota, Haploviricotina, Nidovirales)
• RNA-3'OH (Polynega-type Cap-snatching,Toti-type cap-snatching)
• Protein Vpg

Enzymatic reaction:

• RNA nucleotidyltransferase (RNA-dependent) EC 2.7.7.48RHEA:21248

MechanismViral RdRp are characterized by a conserved motif in which two conserved aspartic acid residues are bound to two magnesium ions. The reaction begins with the deprotonation of primer's 3' OH, in a manner that doesn't require a base. Subsequently, the 3'-oxygen acts as a nucleophile to attack the phosphate bond and eventually releases a pyrophosphate.

MotifsRdRp are characterized by up to six conserved motifs: A,B,C,D,E and F. Motifs A and C carries the catalytic aspartic acids (on orange background).Source:

Identification of four conserved motifs among the RNA-dependent polymerase encoding elements
O Poch 1, I Sauvaget, M Delarue, N Tordo
EMBO J. 1989 Dec 1;8(12):3867-74

A Structural Overview of RNA-Dependent RNA Polymerases from the Flaviviridae Family
Jiqin Wu, Weichi Liu, and Peng Gong
Int J Mol Sci. 2015 Jun; 16(6): 12943?12957

Multiple deprotonation paths of the nucleophile 3'-OH in the DNA synthesis reaction
Mark T Gregory, Yang Gao, Qiang Cui, Wei Yang
Proc Natl Acad Sci U S A. 2021 Jun 8;118(23):e2103990118.