Identification of four conserved motifs among the RNA-dependent polymerase encoding elements.

Abstract

Four consensus sequences are conserved with the same linear arrangement in RNA‐dependent DNA polymerases encoded by retroid elements and in RNA‐dependent RNA polymerases encoded by plus‐, minus‐ and double‐strand RNA viruses. One of these motifs corresponds to the YGDD span previously described by Kamer and Argos (1984). These consensus sequences altogether lead to 4 strictly and 18 conservatively maintained amino acids embedded in a large domain of 120 to 210 amino acids. As judged from secondary structure predictions, each of the 4 motifs, which may cooperate to form a well‐ordered domain, places one invariant amino acid in or proximal to turn structures that may be crucial for their correct positioning in a catalytic process. We suggest that this domain may constitute a prerequisite ‘polymerase module’ implicated in template seating and polymerase activity. At the evolutionary level, the sequence similarities, gap distribution and distances between each motif strongly suggest that the ancestral polymerase module was encoded by an individual genetic element which was most closely related to the plus‐strand RNA viruses and the non‐viral retroposons. This polymerase module gene may have subsequently propagated in the viral kingdom by distinct gene set recombination events leading to the wide viral variety observed today.

Structures of EV71 RNA-dependent RNA polymerase in complex with substrate and analogue provide a drug target against the hand-foot-and-mouth disease pandemic in China

“…Motif A, B, C and D, located in the palm domain, are defined in all classes of polymerases, whereas motif E in the palm domain and motif F in the fingers domain are unique to both RdRps and reverse transcriptases (RTs) (Fig. 1B) (Poch et al, 1989;Hansen et al, 1997;O'Reilly and Kao, 1998). The fingers domain can be further subdivided into five distinct finger motifs, which are named as index, pinky, middle and ring fingers as indicated in the homologous structures in the Picornaviridae family (Ferrer-Orta et al, 2006).…”

Bunyavirus N: eIF4F surrogate and cap-guardian

“…[45][46][47] Recent data indicates that the endonuclease activity for pre-mRNA scission and generation of the capped oligomer resides with PA. 48,49 PB1 has intrinsic polymerase activity and is responsible for both mRNA elongation and correct association with the viral RNA template. 50 In contrast to influenza virus, bunya-and arenavirus replication is exclusively cytoplasmic and caps are thus derived from mRNA rather than pre-mRNA. [51][52][53][54][55][56] Since cellular mRNA degradation also occurs in the cytoplasm this raises the question of the relationship between mRNA decay and the bunya-and arenavirus cap-snatching process.…”

Expression of an active form of recombinant Ty1 reverse transcriptase in Escherichia coli: a fusion protein containing the C-terminal region of the Ty1 integrase linked to the reverse transcriptase–RNase H domain exhibits polymerase and RNase H activities

“…Alignment of the five conserved motifs (A to E, indicated by black bars above the alignment) within the polymerase domain was as described by Poch et al [29]. The nearly invariant amino acid residues found in all RNA-dependent polymerases are underlined.…”

“…The crystal structure of the p66 subunit of HIV-1 RT has shown that the polymerase domain is separated from the RH domain by a connection subdomain which forms a groove between the two active sites and plays a role in binding of the primer-template [22]. Sequence comparison of Ty1 and HIV-1 RTs [29][30][31] shows that the connection domain of the Ty1 enzyme is shorter than the connection domain of the HIV-1 RT (Figure 6). This difference could explain the difference of length of primer-template which can be accommodated between the active sites of the two enzymes.…”