{QDOC50520}
{PS50521}
{PS50507}
{PS50523}
{PS50524}
{PS50525}
{PS50526}
{PS50527}
{BEGIN}
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* RNA-directed RNA polymerase. *
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RNA-directed RNA polymerase (RdRp) (EC 2.7.7.48) is an essential protein encoded in
the genomes of all RNA containing  viruses with no DNA stage. 
It catalyses synthesis of the RNA strand complementary to a given RNA template.

RdRp's of many viruses are products of processing of polyproteins. 
Some RdRp's consist of one polypeptide chain, 
other are complexes of several subunits.

The domain organization [1] and the 3D structure of the catalytic center of 
a wide range of RdPp, even those with a low overall sequence homology, 
are conserved. The catalytic center is formed by several motifs containing 
a number of conservative amino-acid residues.

We developed a set of profiles (PS50521, PS50507, PS50522, PS50523, PS50524,
PS50525, PS50526) for detecting RdRp's (or subunits containing catalitic center 
of RdRp's) of viruses.

There are 4 superfamilies of viruses 
that cover all RNA containing viruses with no DNA stage:

1. Viruses containing positive-strand RNA or 
   double-strand RNA, except of retroviruses and Birnaviridae family. 
   The profile PS50521 corresponds to the segment of 100 - 150 aa of RdRp, 
   which contains three motifs putatively forming the catalytic center. 

   Viruses whose RNA-directed RNA polymerases are 
   described by the profile PS50521 are (see [2,3]):

   - All positive-strand RNA viruses with no DNA stage:
   Arteriviridae, Bromoviridae, Caliciviridae, Comoviridae, 
   Coronaviridae, Flaviviridae, Leviviridae, Luteoviridae, 
   Picornaviridae, Potyviridae, Togaviridae, Tombusviridae,
   Capilloviruses, Carlaviruses, Potexviruses, Tobamoviruses,
   Tobraviruses, Trichoviruses, Tymoviruses, Hepatitis E-like viruses,
   Allexivirus, Sobemovirus.
   
   - double-strand RNA viruses, families Cystoviridae, Reoviridae, 
   Hypoviridae, Partitiviridae, Totiviridae.

2. Order Mononegavirales (negative-strand RNA viruses 
   with non-segmented genome). The profile PS50524 corresponds 
   to the segment of 128 - 141 aa of RdRp, which contains three motifs putatively 
   forming the catalytic center. RdRp's of these viruses can have descriptions: 
   "Large protein", "L protein", "RNA polymerase beta subunit", 
   "Polymerase subunit L". 
   
3. Negative-strand RNA viruses with segmented genome, i.e., 
   Orthomyxoviruses (including influenza A, B, and C viruses,
   Thogotoviruses, and the infectious salmon anemia virus), 
   Arenaviruses, Bunyaviruses, Hantaviruses,
   Nairoviruses, Phleboviruses, Tenuiviruses, and Tospoviruses.

   The profile PS50525 corresponds to a relatively conserved segment of 
   147 - 180 aa of RdRp or its catalitic subunit. 
   The proteins detected by this profile are:
   - RNA polymerase PB1 subunits of Orthomyxoviruses  
   - RNA polymerases (L proteins) of Arenaviruses, Bunyaviruses, Hantaviruses,
     Nairoviruses, Phleboviruses, Tenuiviruses, and Tospoviruses. 

4. Birnaviridae family of dsRNA viruses. The profile PS50526 corresponds 
   to a conservative segment of 105 aa nearly in the middle of 
   the polypepdide chain of RdRp.


We also developed profiles for RdRp's of the following three 
subgroups of the above superfamily 1:

- All positive-strand RNA eukariotic viruses with no DNA stage, profile PS50507.

- All RNA-containing bacteriophages, profile PS50522. There are two families of 
  RNA-containing bacteriophages: Leviviridae (positive ssRNA phages)
  and Cystoviridae (dsRNA phages).

- Reoviridae family of dsRNA viruses, profile PS50523. 


RdRp's of Orthoreoviruses (Reoviridae family) are known as 
"minor core proteins lambda 3" [4]. There are other proteins of Orthoreoviruses, 
sigma NS proteins, which also are annotated as RNA-directed RNA polymerases. 
Sigma NS are relatively small proteins, 366 aa residues long, 
while other RdRp's of Reoviridae are 1088 to 1444 aa residues long. 
Sigma NS proteins of Orthoreoviruses are not described by the profiles.

The RNA polymerase gene of Coronaviridae contains two overlapping
reading frames, ORF1A and ORF1B. Only the products of ORF1B are
described by the profiles.


- Sequences known to belong to this class detected by the profiles: ALL,
  except for ORF1A of Coronaviridae and sigma NS proteins of Orthoreoviruses.
- Other sequence(s) detected in SWISS-PROT: NONE.


1. O'Reilly E.K., Kao C.C. 
   Analysis of RNA-dependent RNA polymerase structure and function as guided 
   by known polymerase structures and computer predictions of secondary structure.
   Virology 252(2):287-303 (1998)
   PMID: 98786

2. NCBI taxonomy browser 
   (http://www.ncbi.nlm.nih.gov/htbin-post/Taxonomy/wgetorg?name=Viruses)

3. Index Virum
   (http://life.anu.edu.au/viruses/Ictv/)

4. Starnes M.C., Joklik W.K. 
   Reovirus protein lambda 3 is a poly(C)-dependent poly(G) polymerase. 
   Virology 193(1):356-366 (1993)