PROSITE documentation PDOC50507 [for PROSITE entry PS50507]

RNA-directed RNA polymerase catalytic domain profiles


RNA-directed RNA polymerase (RdRp) (EC 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 [3].

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>) [4]. 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 [5].

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).


The GDD motif lacks in Birnaviridae RNA-directed RNA polymerases [6].

Last update:

November 2005 / First entry.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

RDRP_SSRNA_POS, PS50507; RdRp of positive ssRNA viruses catalytic domain profile  (MATRIX)

RDRP_DSRNA_BIR, PS50524; RdRp of Birnaviridae dsRNA viruses catalytic domain profile  (MATRIX)

RDRP_DSRNA_REO, PS50523; RdRp of Reoviridae dsRNA viruses catalytic domain profile  (MATRIX)

RDRP_PHAGE, PS50522; RdRp of RNA-containing bacteriophages catalytic domain profile  (MATRIX)

RDRP_SSRNA_NEG_NONSEG, PS50526; RdRp of negative ssRNA viruses with non-segmented genomes catalytic domain profile  (MATRIX)

RDRP_SSRNA_NEG_SEG, PS50525; RdRp of negative ssRNA viruses with segmented genomes catalytic domain profile  (MATRIX)


1AuthorsKoonin E.V., Gorbalenya A.E., Chumakov K.M.
TitleTentative identification of RNA-dependent RNA polymerases of dsRNA viruses and their relationship to positive strand RNA viral polymerases.
SourceFEBS Lett. 252:42-46(1989).
PubMed ID2759231

2AuthorsZanotto P.M., Gibbs M.J., Gould E.A., Holmes E.C.
TitleA reevaluation of the higher taxonomy of viruses based on RNA polymerases.
SourceJ. Virol. 70:6083-6096(1996).
PubMed ID8709232

3AuthorsKao C.C., Singh P., Ecker D.J.
TitleDe novo initiation of viral RNA-dependent RNA synthesis.
SourceVirology 287:251-260(2001).
PubMed ID11531403

4AuthorsHansen J.L., Long A.M., Schultz S.C.
TitleStructure of the RNA-dependent RNA polymerase of poliovirus.
SourceStructure 5:1109-1122(1997).
PubMed ID9309225

5AuthorsGohara D.W., Crotty S., Arnold J.J., Yoder J.D., Andino R., Cameron C.E.
TitlePoliovirus RNA-dependent RNA polymerase (3Dpol): structural, biochemical, and biological analysis of conserved structural motifs A and B.
SourceJ. Biol. Chem. 275:25523-25532(2000).
PubMed ID10827187

6AuthorsShwed P.S., Dobos P., Cameron L.A., Vakharia V.N., Duncan R.
TitleBirnavirus VP1 proteins form a distinct subgroup of RNA-dependent RNA polymerases lacking a GDD motif.
SourceVirology 296:241-250(2002).
PubMed ID12069523

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