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RNA-directed RNA polymerase (RdRp) (EC 18.104.22.168) 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).
The GDD motif lacks in Birnaviridae RNA-directed RNA polymerases .
November 2005 / First entry.
PROSITE methods (with tools and information) covered by this documentation:
Koonin E.V., Gorbalenya A.E., Chumakov K.M.
Tentative identification of RNA-dependent RNA polymerases of dsRNA viruses and their relationship to positive strand RNA viral polymerases.
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