rna directed dna polymerase

Summary

Summary: An enzyme that synthesizes DNA on an RNA template. It is encoded by the pol gene of retroviruses and by certain retrovirus-like elements. EC 2.7.7.49.

Top Publications

  1. Takeuchi R, Certo M, Caprara M, Scharenberg A, Stoddard B. Optimization of in vivo activity of a bifunctional homing endonuclease and maturase reverses evolutionary degradation. Nucleic Acids Res. 2009;37:877-90 pubmed publisher
    ..This implies that mutations that have previously reduced the endonuclease activity of I-AniI are identified and reversed, sometimes in combination with additional 'artificial' mutations, to optimize its in vivo activity. ..
  2. Favre D. Reverse transcriptase activity of hepatitis B virus polymerase in eukaryotic cell extracts in vitro. ALTEX. 2008;25:197-211 pubmed
  3. Baldick C, Tenney D, Mazzucco C, Eggers B, Rose R, Pokornowski K, et al. Comprehensive evaluation of hepatitis B virus reverse transcriptase substitutions associated with entecavir resistance. Hepatology. 2008;47:1473-82 pubmed publisher
    ..The high number of tolerated and resistant ETVr substitutions is consistent with models predicting that the mechanism for ETVr is through enhancement of LVDr changes in the RT deoxyribonucleotide triphosphate (dNTP)-binding pocket. ..
  4. Rösler C, Kock J, Kann M, Malim M, Blum H, Baumert T, et al. APOBEC-mediated interference with hepadnavirus production. Hepatology. 2005;42:301-9 pubmed
    ..In contrast to HIV and other retroviruses, however, APOBEC3G/3F-mediated editing of nucleic acids does not seem to represent an effective innate defense mechanism for hepadnaviruses...
  5. Zhao J, Lambowitz A. A bacterial group II intron-encoded reverse transcriptase localizes to cellular poles. Proc Natl Acad Sci U S A. 2005;102:16133-40 pubmed
    ..coli chromosome, may facilitate access to exposed DNA in these regions, and could potentially link group II intron mobility to the host DNA replication and/or cell division machinery. ..
  6. Held D, Kissel J, Thacker S, Michalowski D, Saran D, Ji J, et al. Cross-clade inhibition of recombinant human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus SIVcpz reverse transcriptases by RNA pseudoknot aptamers. J Virol. 2007;81:5375-84 pubmed
    ..RNA structural diversity therefore translates into a nonoverlapping spectrum of mutations that confer resistance, likely due to differences in atomic-level contacts with RT. ..
  7. Suslov O, Steindler D. PCR inhibition by reverse transcriptase leads to an overestimation of amplification efficiency. Nucleic Acids Res. 2005;33:e181 pubmed
    ..The possible mechanism of RT influence on PCR is presented, and a purification method is implemented to remove the effects of RT on PCR. ..
  8. Downing M, Brady K, Caprara M. A C-terminal fragment of an intron-encoded maturase is sufficient for promoting group I intron splicing. RNA. 2005;11:437-46 pubmed
    ..This fragment of I-AniI represents the smallest group I intron splicing cofactor described to date. ..
  9. Kantor R, Katzenstein D, Efron B, Carvalho A, Wynhoven B, Cane P, et al. Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration. PLoS Med. 2005;2:e112 pubmed
    ..Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations. ..

More Information

Publications62

  1. Cao F, Badtke M, Metzger L, Yao E, Adeyemo B, Gong Y, et al. Identification of an essential molecular contact point on the duck hepatitis B virus reverse transcriptase. J Virol. 2005;79:10164-70 pubmed
    ..Therefore, small-molecule ligands that compete for binding to T3 with its natural ligand could form a novel class of antiviral drugs...
  2. Wilhelm F, Wilhelm M, Gabriel A. Reverse transcriptase and integrase of the Saccharomyces cerevisiae Ty1 element. Cytogenet Genome Res. 2005;110:269-87 pubmed
    ..A focus of this review is to discuss some of the results obtained thus far with these two recombinant proteins and to propose future directions. ..
  3. Christensen S, Bibillo A, Eickbush T. Role of the Bombyx mori R2 element N-terminal domain in the target-primed reverse transcription (TPRT) reaction. Nucleic Acids Res. 2005;33:6461-8 pubmed
    ..Mutations of the protein domain also affected binding of the upstream subunit but not its function, suggesting the primary path to DNA target recognition by R2 involves both upstream and downstream subunits. ..
  4. Wilhelm M, Wilhelm F. Cooperation between reverse transcriptase and integrase during reverse transcription and formation of the preintegrative complex of Ty1. Eukaryot Cell. 2006;5:1760-9 pubmed
    ..Our data support a model in which IN not only interacts closely with RT during reverse transcription but also remains associated with RT during the formation of the preintegrative complex. ..
  5. Hartl M, Kretzschmar B, Frohn A, Nowrouzi A, Rethwilm A, Wohrl B. AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. Nucleic Acids Res. 2008;36:1009-16 pubmed
    ..The additional amino acid change of the quadruple mutant appears to be important for regaining polymerization efficiency. ..
  6. Villet S, Pichoud C, Billioud G, Barraud L, Durantel S, Trepo C, et al. Impact of hepatitis B virus rtA181V/T mutants on hepatitis B treatment failure. J Hepatol. 2008;48:747-55 pubmed publisher
    ..These data emphasize the clinical relevance of genotypic and phenotypic analysis in the management of antiviral drug resistance. ..
  7. Hartl M, W hrl B, R sch P, Schweimer K. The solution structure of the simian foamy virus protease reveals a monomeric protein. J Mol Biol. 2008;381:141-9 pubmed publisher
    ..Dimerization might therefore be triggered by additional viral or cellular factors...
  8. Ong J, Loakes D, Jaroslawski S, Too K, Holliger P. Directed evolution of DNA polymerase, RNA polymerase and reverse transcriptase activity in a single polypeptide. J Mol Biol. 2006;361:537-50 pubmed
    ..Our results suggest that spCSR will be a powerful strategy for the generation of polymerases with altered substrate specificity for applications in nano- and biotechnology and in the enzymatic synthesis of antisense and RNAi probes. ..
  9. Odegrip R, Nilsson A, Haggård Ljungquist E. Identification of a gene encoding a functional reverse transcriptase within a highly variable locus in the P2-like coliphages. J Bacteriol. 2006;188:1643-7 pubmed
    ..The product of one of them exhibits reverse transcriptase activity and blocks infection of phage T5...
  10. Caprara M, Chatterjee P, Solem A, Brady Passerini K, Kaspar B. An allosteric-feedback mechanism for protein-assisted group I intron splicing. RNA. 2007;13:211-22 pubmed
    ..The linkage of these changes to stable binding ensures that the protein and RNA do not get sequestered in nonfunctional complexes. ..
  11. Yasukawa K, Nemoto D, Inouye K. Comparison of the thermal stabilities of reverse transcriptases from avian myeloblastosis virus and Moloney murine leukaemia virus. J Biochem. 2008;143:261-8 pubmed
    ..Thermodynamic analysis indicates that thermal inactivation of AMV RT and MMLV RT is due to the large entropy change of activation for thermal inactivation...
  12. Eickbush T, Jamburuthugoda V. The diversity of retrotransposons and the properties of their reverse transcriptases. Virus Res. 2008;134:221-34 pubmed publisher
    ..The RTs of the non-LTR retrotransposons have several unique properties reflecting their adaptation to a different mechanism of retrotransposition. ..
  13. Kojima K, Kanehisa M. Systematic survey for novel types of prokaryotic retroelements based on gene neighborhood and protein architecture. Mol Biol Evol. 2008;25:1395-404 pubmed publisher
    ..In addition, we found 8 RT genes were associated with clustered regularly interspaced short palindrome repeats (CRISPRs) of the CRISPR-Cas system. These RT genes are likely to work in immunity against RNA phages via cDNA synthesis. ..
  14. Reid P, MacInnes H, Cong M, Heneine W, Garcia Lerma J. Natural resistance of human immunodeficiency virus type 2 to zidovudine. Virology. 2005;336:251-64 pubmed
    ..Our results demonstrate that the activity of AZT on HIV-2 is lower than previously thought, and emphasize the need for novel antiretroviral drugs specific for HIV-2. ..
  15. Goodwin K, Long E, Georgiadis M. A host-guest approach for determining drug-DNA interactions: an example using netropsin. Nucleic Acids Res. 2005;33:4106-16 pubmed
  16. Bibillo A, Lener D, Klarmann G, Le Grice S. Functional roles of carboxylate residues comprising the DNA polymerase active site triad of Ty3 reverse transcriptase. Nucleic Acids Res. 2005;33:171-81 pubmed
    ..Although Asp214 was most insensitive to substitution with respect to activity of the recombinant enzyme, all alterations at this position were lethal for Ty3 transposition. ..
  17. Hu J, Flores D, Toft D, Wang X, Nguyen D. Requirement of heat shock protein 90 for human hepatitis B virus reverse transcriptase function. J Virol. 2004;78:13122-31 pubmed
    ..The establishment of a defined in vitro reconstitution system has now paved the way for future biochemical and structural studies to elucidate the mechanisms of RT-epsilon interaction and chaperone activation...
  18. Beauregard A, Chalamcharla V, Piazza C, Belfort M, Coros C. Bipolar localization of the group II intron Ll.LtrB is maintained in Escherichia coli deficient in nucleoid condensation, chromosome partitioning and DNA replication. Mol Microbiol. 2006;62:709-22 pubmed
    ..Together, these results suggest that bipolar localization of group II intron retrotransposition results from the residence of the intron-encoded protein at the poles of the cell. ..
  19. Santos Velazquez J, Kim B. Deoxynucleoside triphosphate incorporation mechanism of foamy virus (FV) reverse transcriptase: implications for cell tropism of FV. J Virol. 2008;82:8235-8 pubmed publisher
    ..These three RTs, however, show similar catalytic activities. In conclusion, PFV RT displays mechanistic distinctions in comparison to HIV-1 RT and shares close similarity to MuLV RT...
  20. Roy S, Irimia M. When good transcripts go bad: artifactual RT-PCR 'splicing' and genome analysis. Bioessays. 2008;30:601-5 pubmed publisher
    ..Supplementary material for this article can be found on the BioEssays website (http://www.interscience.wiley.com/jpages/0265-9247/suppmat/index.html). ..
  21. Roy J, Linial M. Role of the foamy virus Pol cleavage site in viral replication. J Virol. 2007;81:4956-62 pubmed
    ..Interestingly, Pol encapsidation is significantly reduced in some of the mutants...
  22. Beck J, Nassal M. Hepatitis B virus replication. World J Gastroenterol. 2007;13:48-64 pubmed
    ..The ultimate, though most challenging goal, will be to visualize the hepadnaviral reverse transcriptase in the act of synthesizing DNA, which will also have strong implications for drug development...
  23. Sauter K, Marx A. Evolving thermostable reverse transcriptase activity in a DNA polymerase scaffold. Angew Chem Int Ed Engl. 2006;45:7633-5 pubmed
  24. Colson P, Henry M, Tivoli N, Gallais H, Gastaut J, Moreau J, et al. Polymorphism and drug-selected mutations in the reverse transcriptase gene of HIV-2 from patients living in southeastern France. J Med Virol. 2005;75:381-90 pubmed
    ..As in HIV-1, substitution M184V was found in 3TC-treated patients. In conclusion, these findings highlight the need for specific guidelines for determining genotypic resistance and treatment of HIV-2. ..
  25. Vichier Guerre S, Ferris S, Auberger N, Mahiddine K, Jestin J. A population of thermostable reverse transcriptases evolved from Thermus aquaticus DNA polymerase I by phage display. Angew Chem Int Ed Engl. 2006;45:6133-7 pubmed
  26. Boyer P, Sarafianos S, Clark P, Arnold E, Hughes S. Why do HIV-1 and HIV-2 use different pathways to develop AZT resistance?. PLoS Pathog. 2006;2:e10 pubmed
    ..Thus, each RT usually chooses the pathway best suited to extend the properties of the respective wild-type enzymes. ..
  27. Hu J, Boyer M. Hepatitis B virus reverse transcriptase and epsilon RNA sequences required for specific interaction in vitro. J Virol. 2006;80:2141-50 pubmed publisher
    ..In addition, our results suggest that recognition of some epsilon sequences by the RT may be required specifically for viral DNA synthesis...
  28. Cocquet J, Chong A, Zhang G, Veitia R. Reverse transcriptase template switching and false alternative transcripts. Genomics. 2006;88:127-31 pubmed
    ..However, care should be taken in the annotation of alternative transcripts, especially when the RT used is poorly thermostable and when the putative intron is flanked by direct repeats, which are the substrate for template switching. ..
  29. Blocker F, Mohr G, Conlan L, Qi L, Belfort M, Lambowitz A. Domain structure and three-dimensional model of a group II intron-encoded reverse transcriptase. RNA. 2005;11:14-28 pubmed
    ..These regions potentially comprise an extended RNA-binding surface that interacts with different regions of the intron for RNA splicing and reverse transcription. ..
  30. Christensen S, Eickbush T. R2 target-primed reverse transcription: ordered cleavage and polymerization steps by protein subunits asymmetrically bound to the target DNA. Mol Cell Biol. 2005;25:6617-28 pubmed
    ..A complete model for the R2 integration reaction is presented, which with minor modifications is adaptable to other non-LTR retrotransposons. ..
  31. Fortier L, Bouchard J, Moineau S. Expression and site-directed mutagenesis of the lactococcal abortive phage infection protein AbiK. J Bacteriol. 2005;187:3721-30 pubmed publisher
    ..These data suggest that an RT activity might be involved in the phage resistance activity of AbiK. A model for the mode of action of AbiK is proposed...
  32. Kissel J, Held D, Hardy R, Burke D. Single-stranded DNA aptamer RT1t49 inhibits RT polymerase and RNase H functions of HIV type 1, HIV type 2, and SIVCPZ RTs. AIDS Res Hum Retroviruses. 2007;23:699-708 pubmed
    ..This is the first demonstration of universal inhibition of HIV and SIV(cpz) RTs by a nucleic acid aptamer and supports previous reports suggesting that resistance to RT1t49 may be exceptionally infrequent. ..
  33. Aizawa Y, Xiang Q, Lambowitz A, Pyle A. The pathway for DNA recognition and RNA integration by a group II intron retrotransposon. Mol Cell. 2003;11:795-805 pubmed
    ..Group II mobility must therefore depend on the trapping of invasion products, potentially through interaction of the intron-encoded protein with the DNA target and/or initiation of reverse transcription. ..
  34. Fisher T, Darden T, Prasad V. Mutations proximal to the minor groove-binding track of human immunodeficiency virus type 1 reverse transcriptase differentially affect utilization of RNA versus DNA as template. J Virol. 2003;77:5837-45 pubmed
  35. Lehmann K, Schmidt U. Group II introns: structure and catalytic versatility of large natural ribozymes. Crit Rev Biochem Mol Biol. 2003;38:249-303 pubmed
  36. Kelly N, Morrow C. Yeast tRNA(Phe) expressed in human cells can be selected by HIV-1 for use as a reverse transcription primer. Virology. 2003;313:354-63 pubmed
    ..The results of these studies demonstrate that intracellular levels of primer tRNA can have a direct effect on HIV-1 infectivity and further support the role for PBS-tRNA complementarity in the primer selection process. ..
  37. Permanyer J, Gonzalez Duarte R, Albalat R. The non-LTR retrotransposons in Ciona intestinalis: new insights into the evolution of chordate genomes. Genome Biol. 2003;4:R73 pubmed
    ..The analysis provides valuable data for understanding the evolution of early chordate genomes and enlarges the view on the distribution of the non-LTR retrotransposons in eukaryotes. ..
  38. Dumans A, Soares M, Machado E, Hue S, Brindeiro R, Pillay D, et al. Synonymous genetic polymorphisms within Brazilian human immunodeficiency virus Type 1 subtypes may influence mutational routes to drug resistance. J Infect Dis. 2004;189:1232-8 pubmed
    ..The findings of the present study illustrate an important mechanism by which a subtype may determine genetic routes to resistance, with implications for treatment strategies for populations infected with HIV-1 subtype F. ..
  39. Pandey M, Patel S, Gabriel A. Insights into the role of an active site aspartate in Ty1 reverse transcriptase polymerization. J Biol Chem. 2004;279:47840-8 pubmed
    ..These results provide insights to specific roles for the Asp(211) residue during polymerization and indicate unusual enzymatic properties that bear on the Ty1 replication pathway. ..
  40. Geese W, Kwon Y, Wen X, Waring R. In vitro analysis of the relationship between endonuclease and maturase activities in the bi-functional group I intron-encoded protein, I-AniI. Eur J Biochem. 2003;270:1543-54 pubmed
    ..The data suggest therefore that both nucleic acids do not bind the same single binding site, rather that I-AniI appears to contain two binding sites. ..
  41. Christensen S, Eickbush T. Footprint of the retrotransposon R2Bm protein on its target site before and after cleavage. J Mol Biol. 2004;336:1035-45 pubmed
    ..We suggest that this increased protection after cleavage is the RT domain that is positioned over the free DNA end to begin reverse transcription on the nicked DNA substrate. ..
  42. Ståhlberg A, Kubista M, Pfaffl M. Comparison of reverse transcriptases in gene expression analysis. Clin Chem. 2004;50:1678-80 pubmed
  43. Post K, Guo J, Howard K, Powell M, Miller J, Hizi A, et al. Human immunodeficiency virus type 2 reverse transcriptase activity in model systems that mimic steps in reverse transcription. J Virol. 2003;77:7623-34 pubmed
    ..This may reflect architectural differences in the primer grip regions in the p66 (HIV-1) and p68 (HIV-2) palm subdomains of the two enzymes. The implications of our findings for antiviral therapy are discussed. ..
  44. Shandilya H, Griffiths K, Flynn E, Astatke M, Shih P, Lee J, et al. Thermophilic bacterial DNA polymerases with reverse-transcriptase activity. Extremophiles. 2004;8:243-51 pubmed
    ..Several enzymes showed significant reverse-transcriptase activity in the presence of Mg2+, particularly the polymerases from Bacillus caldolyticus EA1, Caldibacillus cellovorans CompA.2, and Clostridium stercorarium. ..
  45. Lener D, Kvaratskhelia M, Le Grice S. Nonpolar thymine isosteres in the Ty3 polypurine tract DNA template modulate processing and provide a model for its recognition by Ty3 reverse transcriptase. J Biol Chem. 2003;278:26526-32 pubmed
  46. Boyer P, Stenbak C, Clark P, Linial M, Hughes S. Characterization of the polymerase and RNase H activities of human foamy virus reverse transcriptase. J Virol. 2004;78:6112-21 pubmed
    ..Although the sequence of the basic loop of FV RT is different from the basic loop of either Moloney leukemia virus RNase H or Escherichia coli RNase H, the FV RT basic loop appears to have a similar function. ..
  47. Ruschak A, Mathews D, Bibillo A, Spinelli S, Childs J, Eickbush T, et al. Secondary structure models of the 3' untranslated regions of diverse R2 RNAs. RNA. 2004;10:978-87 pubmed
    ..The structures appear to have common helices that are likely important for function. ..
  48. Doulatov S, Hodes A, Dai L, Mandhana N, Liu M, Deora R, et al. Tropism switching in Bordetella bacteriophage defines a family of diversity-generating retroelements. Nature. 2004;431:476-81 pubmed
    ..These elements constitute a new family of retroelements with the potential to confer selective advantages to their host genomes. ..
  49. Bartholomeusz A, Tehan B, Chalmers D. Comparisons of the HBV and HIV polymerase, and antiviral resistance mutations. Antivir Ther. 2004;9:149-60 pubmed
    ..In addition, the antiviral resistance mutations including potential compensatory mutations were mapped to determine their effect on the HBV polymerase model, especially in the nucleotide binding site. ..
  50. Rethwilm A. The replication strategy of foamy viruses. Curr Top Microbiol Immunol. 2003;277:1-26 pubmed
    ..A number of experimental findings in favour of the view that foamy viruses are reverse transcribing DNA viruses which integrate into the host cell genome are discussed...
  51. Beck J, Nassal M. Efficient Hsp90-independent in vitro activation by Hsc70 and Hsp40 of duck hepatitis B virus reverse transcriptase, an assumed Hsp90 client protein. J Biol Chem. 2003;278:36128-38 pubmed
    ..Thus Hsc70, mostly known for its role in general protein folding, is able to effect activation of a highly specialized target protein...
  52. Bibillo A, Eickbush T. End-to-end template jumping by the reverse transcriptase encoded by the R2 retrotransposon. J Biol Chem. 2004;279:14945-53 pubmed
    ..These end-to-end jumps are similar to steps proposed to be part of the integration reaction of non-long terminal repeat retrotransposons and can explain chimeric integration products derived from multiple RNA templates. ..
  53. Tenney D, Levine S, Rose R, Walsh A, Weinheimer S, Discotto L, et al. Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to Lamivudine. Antimicrob Agents Chemother. 2004;48:3498-507 pubmed
    ..In summary, infrequent ETV resistance can emerge during prolonged therapy, with selection of additional RT substitutions within a 3TC(r) HBV background, leading to reduced ETV susceptibility and treatment failure. ..