|PROSITE documentation PDOC50507|
RNA-directed RNA polymerase (RdRp) (EC 22.214.171.124) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage [1,2]. It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear. The postulated 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) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (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 .
All the RNA-directed RNA polymerases, and many DNA-directed polymerases, employ a fold whose organization has been likened to the shape of a right hand with three subdomains termed fingers, palm and thumb (see <PDB:1RDR>) . Only the palm subdomain, composed of a four-stranded antiparallel β-sheet with two α-helices, is well conserved among all of these enzymes. In RdRp, the palm subdomain comprises three well conserved motifs (A, B and C). Motif A (D-x(4,5)-D) and motif C (GDD) are spatially juxtaposed; the Asp residues of these motifs are implied in the binding of Mg2+ and/or Mn2+. The Asn residue of motif B is involved in selection of ribonucleoside triphosphates over dNTPs and thus determines whether RNA is synthesized rather than DNA .
RNA viruses with no DNA stage can be placed in three main categories based on their replication and coding strategies: positive single-stranded RNA (ssRNA), negative ssRNA and double-stranded RNA (dsRNA) viruses. To recognize RNA-directed RNA polymerase we have developed six profiles that roughly follow this classification (see below). They are all directed against the catalytic region (palm subdomain).Note:
The GDD motif lacks in Birnaviridae RNA-directed RNA polymerases .Last update:
November 2005 / First entry.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Koonin E.V. Gorbalenya A.E. Chumakov K.M.|
|Title||Tentative identification of RNA-dependent RNA polymerases of dsRNA viruses and their relationship to positive strand RNA viral polymerases.|
|Source||FEBS Lett. 252:42-46(1989).|
|2||Authors||Zanotto P.M. Gibbs M.J. Gould E.A. Holmes E.C.|
|Title||A reevaluation of the higher taxonomy of viruses based on RNA polymerases.|
|Source||J. Virol. 70:6083-6096(1996).|
|3||Authors||Kao C.C. Singh P. Ecker D.J.|
|Title||De novo initiation of viral RNA-dependent RNA synthesis.|
|4||Authors||Hansen J.L. Long A.M. Schultz S.C.|
|Title||Structure of the RNA-dependent RNA polymerase of poliovirus.|
|5||Authors||Gohara D.W. Crotty S. Arnold J.J. Yoder J.D. Andino R. Cameron C.E.|
|Title||Poliovirus RNA-dependent RNA polymerase (3Dpol): structural, biochemical, and biological analysis of conserved structural motifs A and B.|
|Source||J. Biol. Chem. 275:25523-25532(2000).|
|6||Authors||Shwed P.S. Dobos P. Cameron L.A. Vakharia V.N. Duncan R.|
|Title||Birnavirus VP1 proteins form a distinct subgroup of RNA-dependent RNA polymerases lacking a GDD motif.|