Genomes and Genes
Summary: An enzyme that catalyses RNA-template-directed extension of the 3'- end of an RNA strand by one nucleotide at a time, and can initiate a chain de novo. (Enzyme Nomenclature, 1992, p293)
- DuBois R, Slavish P, Baughman B, Yun M, Bao J, Webby R, et al. Structural and biochemical basis for development of influenza virus inhibitors targeting the PA endonuclease. PLoS Pathog. 2012;8:e1002830 pubmed publisher..Taken together, our data reveal new strategies for structure-based design and optimization of PA endonuclease inhibitors. ..
- Subba Reddy C, Goodfellow I, Kao C. VPg-primed RNA synthesis of norovirus RNA-dependent RNA polymerases by using a novel cell-based assay. J Virol. 2011;85:13027-37 pubmed publisher..The assay should be useful for the dissection of the requirements for NoV RNA synthesis as well as the identification of inhibitors of the NoV RdRp. ..
- Mine A, Okuno T. Composition of plant virus RNA replicase complexes. Curr Opin Virol. 2012;2:669-75 pubmed publisherThe replication of the genome of positive-strand RNA viruses depends on their own RNA replicase complexes...
- Rajeswaran R, Pooggin M. RDR6-mediated synthesis of complementary RNA is terminated by miRNA stably bound to template RNA. Nucleic Acids Res. 2012;40:594-9 pubmed publisher..The short, but not long, overhang is optimal for DCL4 binding, which ensures dsRNA processing from one end into phased siRNA duplexes with 2-nt 3'-overhangs. ..
- Zhang S, Wang Q, Wang J, Mizumoto K, Toyoda T. Two mutations in the C-terminal domain of influenza virus RNA polymerase PB2 enhance transcription by enhancing cap-1 RNA binding activity. Biochim Biophys Acta. 2012;1819:78-83 pubmed publisher..These mutations at the C-terminal domain of PB2 may affect its cap-binding domain...
- Selisko B, Potisopon S, Agred R, Priet S, Varlet I, Thillier Y, et al. Molecular basis for nucleotide conservation at the ends of the dengue virus genome. PLoS Pathog. 2012;8:e1002912 pubmed publisher..This can be regarded as a genomic/antigenomic RNA end repair mechanism. These conservational mechanisms, mediated by the polymerase alone, may extend to other RNA virus families having RdRps initiating RNA synthesis de novo. ..
- Thivierge C, Makil N, Flamand M, Vasale J, Mello C, Wohlschlegel J, et al. Tudor domain ERI-5 tethers an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi. Nat Struct Mol Biol. 2011;19:90-7 pubmed publisher..Our results implicate tudor proteins in the recruitment of RdRP complexes to specific steps within DCR-1-dependent and DCR-1-independent endo-RNAi pathways. ..
- Troke P, Lewis M, Simpson P, Gore K, Hammond J, Craig C, et al. Characterization of resistance to the nonnucleoside NS5B inhibitor filibuvir in hepatitis C virus-infected patients. Antimicrob Agents Chemother. 2012;56:1331-41 pubmed publisher..Amino acid variants at position M423 in HCV NS5B polymerase are the preferred pathway for selection of viral resistance to filibuvir in vivo. ..
- Kortus M, Kempf B, Haworth K, Barton D, Peersen O. A template RNA entry channel in the fingers domain of the poliovirus polymerase. J Mol Biol. 2012;417:263-78 pubmed publisher..These data identify key residues within the template RNA entry channel and begin to define their distinct mechanistic roles within RNA ECs...
- Pathak K, Pogany J, Xu K, White K, Nagy P. Defining the roles of cis-acting RNA elements in tombusvirus replicase assembly in vitro. J Virol. 2012;86:156-71 pubmed publisher..Collectively, this work has revealed new functions for tombusvirus cis-acting RNA elements and provided insights into the pioneering round of minus-strand synthesis...
- Elsayed A, Boulila M, Komor E, Zhu Y. Putative recombination signature and significance of insertion/deletion events in the RNA-dependent RNA polymerase coding region of sugarcane yellow leaf virus. Biochimie. 2012;94:1764-72 pubmed publisher..It is noteworthy that according both methods Haw73-6110 was found as a potential recombinant. On the other hand, opposed to the RDP package, RECCO revealed that Haw87-4094 isolate was also a recombinant whereas Haw87-4319 was not. ..
- Jin Z, Leveque V, Ma H, Johnson K, Klumpp K. Assembly, purification, and pre-steady-state kinetic analysis of active RNA-dependent RNA polymerase elongation complex. J Biol Chem. 2012;287:10674-83 pubmed publisher..This work establishes a novel way to generate a highly active elongation complex of the medically important NS5B polymerase for structural and functional studies. ..
- Russell C, Fonville J, Brown A, Burke D, Smith D, James S, et al. The potential for respiratory droplet-transmissible A/H5N1 influenza virus to evolve in a mammalian host. Science. 2012;336:1541-7 pubmed publisher..These results highlight critical areas in which more data are needed for assessing, and potentially averting, this threat...
- Wiegand S, Hammann C. The 5' spreading of small RNAs in Dictyostelium discoideum depends on the RNA-dependent RNA polymerase RrpC and on the dicer-related nuclease DrnB. PLoS ONE. 2013;8:e64804 pubmed publisher..Thus, our data indicate that transitivity of an RNA silencing signal exists in D. discoideum and that it requires the two enzymes RrpC and DrnB...
- Perez J, Zlatev I, Aggarwal S, Subramanian S, Sachidanandam R, Kim B, et al. A small-RNA enhancer of viral polymerase activity. J Virol. 2012;86:13475-85 pubmed publisher..Taking these observations together, we mechanistically define svRNA as a small regulatory enhancer RNA, which functions to promote genome replication and maintain segment balance through allosteric modulation of polymerase activity. ..
- Gnädig N, Beaucourt S, Campagnola G, Borderia A, Sanz Ramos M, Gong P, et al. Coxsackievirus B3 mutator strains are attenuated in vivo. Proc Natl Acad Sci U S A. 2012;109:E2294-303 pubmed publisher..Our work forges ground in showing that the mutability of RNA viruses does have an upper limit, where larger than natural genetic diversity is deleterious to virus survival. ..
- Noble E, Cox A, Deval J, Kim B. Endonuclease substrate selectivity characterized with full-length PA of influenza A virus polymerase. Virology. 2012;433:27-34 pubmed publisher..Finally, we confirmed the observed endonuclease activity of the full-length PA with a FRET-based assay. ..
- Kowalinski E, Zubieta C, Wolkerstorfer A, Szolar O, Ruigrok R, Cusack S. Structural analysis of specific metal chelating inhibitor binding to the endonuclease domain of influenza pH1N1 (2009) polymerase. PLoS Pathog. 2012;8:e1002831 pubmed publisher..These results will be important in optimising the design of more potent inhibitors targeting the cap-snatching endonuclease activity of influenza virus polymerase. ..
- Seyer R, Hrincius E, Ritzel D, Abt M, Mellmann A, Marjuki H, et al. Synergistic adaptive mutations in the hemagglutinin and polymerase acidic protein lead to increased virulence of pandemic 2009 H1N1 influenza A virus in mice. J Infect Dis. 2012;205:262-71 pubmed publisher..In conclusion, synergistic action of all 3 mutations results in a mice lethal pandemic H1N1 virus. ..
- Kiseleva I, Voeten J, Teley L, Larionova N, Drieszen van der Cruijsen S, Basten S, et al. PB2 and PA genes control the expression of the temperature-sensitive phenotype of cold-adapted B/USSR/60/69 influenza master donor virus. J Gen Virol. 2010;91:931-7 pubmed publisher..This suggests that mutations in the polymerase genes PB2 and PA play an essential role in attenuation of B/USSR/60/69 MDV-based reassortant influenza B vaccine viruses. ..
- Li Z, Pogany J, Tupman S, Esposito A, Kinzy T, Nagy P. Translation elongation factor 1A facilitates the assembly of the tombusvirus replicase and stimulates minus-strand synthesis. PLoS Pathog. 2010;6:e1001175 pubmed publisher..These roles for eEF1A are separate from its canonical role in host and viral protein translation, emphasizing critical functions for this abundant cellular protein during TBSV replication. ..
- Olson A, Rosenblum E, Kuchta R. Regulation of influenza RNA polymerase activity and the switch between replication and transcription by the concentrations of the vRNA 5' end, the cap source, and the polymerase. Biochemistry. 2010;49:10208-15 pubmed publisher..These data provide insights into the regulation of RdRp throughout the viral life cycle and how it synthesizes the appropriate amounts of viral mRNA and replication products (vRNA and cRNA). ..
- Mok C, Yen H, Yu M, Yuen K, Sia S, Chan M, et al. Amino acid residues 253 and 591 of the PB2 protein of avian influenza virus A H9N2 contribute to mammalian pathogenesis. J Virol. 2011;85:9641-5 pubmed publisher..Taken together, our studies help define the viral genetic determinants that contribute to pathogenicity of H9N2 viruses. ..
- Maida Y, Masutomi K. RNA-dependent RNA polymerases in RNA silencing. Biol Chem. 2011;392:299-304 pubmed publisher..These findings suggest that endogenous small interfering RNAs are produced by several mechanisms in eukaryotes. ..
- Wochner A, Attwater J, Coulson A, Holliger P. Ribozyme-catalyzed transcription of an active ribozyme. Science. 2011;332:209-12 pubmed publisher..This recapitulates a central aspect of an RNA-based genetic system: the RNA-catalyzed synthesis of an active ribozyme from an RNA template. ..
- Lee J, Alam I, Han K, Cho S, Shin S, Kang S, et al. Crystal structures of murine norovirus-1 RNA-dependent RNA polymerase. J Gen Virol. 2011;92:1607-16 pubmed publisher..The information gained on the structural and functional features of MNV-1 RdRp will be helpful in understanding replication of norovirus and in designing novel therapeutic agents against this important pathogen. ..
- Ahmed Belkacem A, Ahnou N, Barbotte L, Wychowski C, Pallier C, Brillet R, et al. Silibinin and related compounds are direct inhibitors of hepatitis C virus RNA-dependent RNA polymerase. Gastroenterology. 2010;138:1112-22 pubmed publisher..Our results provide a basis for the optimization and subsequent development of members of the Flavonoid family as specific HCV antivirals. ..
- Aggarwal S, Dewhurst S, Takimoto T, Kim B. Biochemical impact of the host adaptation-associated PB2 E627K mutation on the temperature-dependent RNA synthesis kinetics of influenza A virus polymerase complex. J Biol Chem. 2011;286:34504-13 pubmed publisher..In conclusion, our study suggests that the amino acid sequence variations at residue 627 of PB2 subunit can directly alter the enzyme kinetics of influenza polymerase...
- Ranjith Kumar C, Wen Y, Baxter N, Bhardwaj K, Cheng Kao C. A cell-based assay for RNA synthesis by the HCV polymerase reveals new insights on mechanism of polymerase inhibitors and modulation by NS5A. PLoS ONE. 2011;6:e22575 pubmed publisher..In summary, the 5BR assay could be used to validate inhibitors of the HCV polymerase as well as to elucidate requirements for HCV-dependent RNA synthesis. ..
- Gent J, Schvarzstein M, Villeneuve A, Gu S, Jantsch V, Fire A, et al. A Caenorhabditis elegans RNA-directed RNA polymerase in sperm development and endogenous RNA interference. Genetics. 2009;183:1297-314 pubmed publisher..These and other data suggest a working model in which a major role of the RRF-3/ERI pathway is to generate siRNAs that set patterns of gene expression through feedback repression of a set of critical targets during spermatogenesis. ..
- Cuperus J, Carbonell A, Fahlgren N, Garcia Ruiz H, Burke R, Takeda A, et al. Unique functionality of 22-nt miRNAs in triggering RDR6-dependent siRNA biogenesis from target transcripts in Arabidopsis. Nat Struct Mol Biol. 2010;17:997-1003 pubmed publisher..These data suggest that AGO1 functions differentially with 21- and 22-nt miRNAs to engage the RDR6-associated amplification apparatus. ..
- Wang Y, Shi H, Rigolet P, Wu N, Zhu L, Xi X, et al. Nsp1 proteins of group I and SARS coronaviruses share structural and functional similarities. Infect Genet Evol. 2010;10:919-24 pubmed publisher..However, nsp1 may not be the key determinant of viral pathogenicity, or the factor used by the SARS coronavirus to evade host innate immunity. ..
- Deore R, Chern J. NS5B RNA dependent RNA polymerase inhibitors: the promising approach to treat hepatitis C virus infections. Curr Med Chem. 2010;17:3806-26 pubmed
- Giordano M, Martinez L, Masachessi G, Barril P, Ferreyra L, Isa M, et al. Evidence of closely related picobirnavirus strains circulating in humans and pigs in Argentina. J Infect. 2011;62:45-51 pubmed publisher..On the basis of the published literature, it is still difficult to draw conclusions as to whether picobirnavirus (PBV) circulation is influenced by host species restriction...
- Sakabe S, Ozawa M, Takano R, Iwastuki Horimoto K, Kawaoka Y. Mutations in PA, NP, and HA of a pandemic (H1N1) 2009 influenza virus contribute to its adaptation to mice. Virus Res. 2011;158:124-9 pubmed publisher..Our results suggest the importance of the viral polymerase complex and of HA in viral adaption to a new host. ..
- Zhang S, Wang J, Wang Q, Toyoda T. Internal initiation of influenza virus replication of viral RNA and complementary RNA in vitro. J Biol Chem. 2010;285:41194-201 pubmed publisher..This was because primers overlapping with the first U of the clusters did not initiate transcription efficiently, and the initiation product of v84+G (the v84 template with an extra G at its 3'-end), AGC, realigned to the 3'-end. ..
- Qu F. Antiviral role of plant-encoded RNA-dependent RNA polymerases revisited with deep sequencing of small interfering RNAs of virus origin. Mol Plant Microbe Interact. 2010;23:1248-52 pubmed publisher..In conclusion, these studies established that RDR1 and RDR6 function synergistically to contain RNA virus infections through the RNA silencing-based antiviral defense. ..
- Li Z, Nagy P. Diverse roles of host RNA binding proteins in RNA virus replication. RNA Biol. 2011;8:305-15 pubmed..Altogether, a deeper understanding of the functions of the host RBPs subverted for viral replication will help development of novel antiviral strategies and give new insights into host RNA biology. ..
- Tajima Y, Iwakawa H, Kaido M, Mise K, Okuno T. A long-distance RNA-RNA interaction plays an important role in programmed -1 ribosomal frameshifting in the translation of p88 replicase protein of Red clover necrotic mosaic virus. Virology. 2011;417:169-78 pubmed publisher..The existence of RNA elements responsible for -1 PRF and the cap-independent translation of replicase proteins in the 3' UTR of RNA1 might be important for switching translation to replication and for regulating the ratio of p88 to p27...
- Lam A, Murakami E, Espiritu C, Steuer H, Niu C, Keilman M, et al. PSI-7851, a pronucleotide of beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine monophosphate, is a potent and pan-genotype inhibitor of hepatitis C virus replication. Antimicrob Agents Chemother. 2010;54:3187-96 pubmed publisher..Clearance studies using replicon cells demonstrated that PSI-7851 was able to clear cells of HCV replicon RNA and prevent viral rebound. ..
- Claycomb J, Batista P, Pang K, Gu W, Vasale J, Van Wolfswinkel J, et al. The Argonaute CSR-1 and its 22G-RNA cofactors are required for holocentric chromosome segregation. Cell. 2009;139:123-34 pubmed publisher..Instead, our findings support a model in which CSR-1 complexes target protein-coding domains to promote their proper organization within the holocentric chromosomes of C. elegans. ..
- Schmitt M, Scrima N, Radujkovic D, Caillet Saguy C, Simister P, Friebe P, et al. A comprehensive structure-function comparison of hepatitis C virus strain JFH1 and J6 polymerases reveals a key residue stimulating replication in cell culture across genotypes. J Virol. 2011;85:2565-81 pubmed publisher..Finally, we were able to enhance the replication efficiency of a genotype 1b isolate with the I405 mutation, indicating that this mechanism of action is conserved across genotypes. ..
- te Velthuis A, van den Worm S, Sims A, Baric R, Snijder E, van Hemert M. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010;6:e1001176 pubmed publisher..By chelating Zn(2+) with MgEDTA, the inhibitory effect of the divalent cation could be reversed, which provides a novel experimental tool for in vitro studies of the molecular details of nidovirus replication and transcription...
- Lee H, Aalto A, Yang Q, Chang S, Huang G, Fisher D, et al. The DNA/RNA-dependent RNA polymerase QDE-1 generates aberrant RNA and dsRNA for RNAi in a process requiring replication protein A and a DNA helicase. PLoS Biol. 2010;8: pubmed publisher..Together, these results suggest a novel small RNA biogenesis pathway in Neurospora and a new mechanism for the production of aRNA and dsRNA in RNAi pathways. ..
- Foeglein g, Loucaides E, Mura M, Wise H, Barclay W, Digard P. Influence of PB2 host-range determinants on the intranuclear mobility of the influenza A virus polymerase. J Gen Virol. 2011;92:1650-61 pubmed publisher..While we cannot distinguish between positive and inhibitory effects, the data have implications for how such factors might operate...
- Iwai A, Shiozaki T, Kawai T, Akira S, Kawaoka Y, Takada A, et al. Influenza A virus polymerase inhibits type I interferon induction by binding to interferon beta promoter stimulator 1. J Biol Chem. 2010;285:32064-74 pubmed publisher..These findings demonstrate that the viral polymerase plays an important role for regulating host anti-viral response through the binding to IPS-1 and inhibition of IFN? production. ..
- Cheng C, Shipps G, Yang Z, Kawahata N, Lesburg C, Duca J, et al. Inhibitors of hepatitis C virus polymerase: synthesis and characterization of novel 2-oxy-6-fluoro-N-((S)-1-hydroxy-3-phenylpropan-2-yl)-benzamides. Bioorg Med Chem Lett. 2010;20:2119-24 pubmed publisher..These data warrant further lead optimization efforts on this novel series of non-nucleoside inhibitors targeting the HCV polymerase. ..
- Ruigrok R, Crepin T, Hart D, Cusack S. Towards an atomic resolution understanding of the influenza virus replication machinery. Curr Opin Struct Biol. 2010;20:104-13 pubmed publisher..These results provide the first detailed structure-function insights into polymerase assembly, transcription and host adaptation and will have an impact on anti-influenza drug design. ..