rna cap analogs

Summary

Summary: Analogs of RNA cap compounds which do not have a positive charge. These compounds inhibit the initiation of translation of both capped and uncapped messenger RNA.

Top Publications

  1. Wallace A, Filbin M, Veo B, McFarland C, Stepinski J, Jankowska Anyszka M, et al. The nematode eukaryotic translation initiation factor 4E/G complex works with a trans-spliced leader stem-loop to enable efficient translation of trimethylguanosine-capped RNAs. Mol Cell Biol. 2010;30:1958-70 pubmed publisher
  2. Izaurralde E, Lewis J, McGuigan C, Jankowska M, Darzynkiewicz E, Mattaj I. A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell. 1994;78:657-68 pubmed
    ..Extracts immunodepleted of CBC do not efficiently splice an adenoviral pre-mRNA owing to blockage of an early step in splicing complex formation. CBC may therefore play a role in pre-mRNA recognition. ..
  3. Ahola T, Laakkonen P, Vihinen H, Kaariainen L. Critical residues of Semliki Forest virus RNA capping enzyme involved in methyltransferase and guanylyltransferase-like activities. J Virol. 1997;71:392-7 pubmed
    ..Secondary structure predictions of nsP1 and other proteins of the superfamily place these residues in positions corresponding to AdoMet-binding sites of cellular methyltransferases, suggesting that they all may be structurally related...
  4. Kowalska J, Lukaszewicz M, Zuberek J, Ziemniak M, Darzynkiewicz E, Jemielity J. Phosphorothioate analogs of m7GTP are enzymatically stable inhibitors of cap-dependent translation. Bioorg Med Chem Lett. 2009;19:1921-5 pubmed publisher
    ..Both analogs were also significantly more stable in RRL than unmodified ones. ..
  5. Hooker L, Sully R, Handa B, Ono N, Koyano H, Klumpp K. Quantitative analysis of influenza virus RNP interaction with RNA cap structures and comparison to human cap binding protein eIF4E. Biochemistry. 2003;42:6234-40 pubmed
    ..Due to this difference in cap subsite interaction, it was possible to identify novel cap analogues, which selectively interact with influenza virus, but not human cap binding protein. ..
  6. Ruszczynska K, Kamieńska Trela K, Wojcik J, Stepinski J, Darzynkiewicz E, Stolarski R. Charge distribution in 7-methylguanine regarding cation-pi interaction with protein factor eIF4E. Biophys J. 2003;85:1450-6 pubmed
  7. Grudzien E, Stepinski J, Jankowska Anyszka M, Stolarski R, Darzynkiewicz E, Rhoads R. Novel cap analogs for in vitro synthesis of mRNAs with high translational efficiency. RNA. 2004;10:1479-87 pubmed
    ..The measurement of all five parameters provides insight into factors that contribute to translational efficiency. ..
  8. Brown C, McNae I, Fischer P, Walkinshaw M. Crystallographic and mass spectrometric characterisation of eIF4E with N7-alkylated cap derivatives. J Mol Biol. 2007;372:7-15 pubmed
    ..This and other observations made here will be useful in the design of new families of eIF4E inhibitors, which may have potential therapeutic applications in cancer. ..
  9. Egloff M, Decroly E, Malet H, Selisko B, Benarroch D, Ferron F, et al. Structural and functional analysis of methylation and 5'-RNA sequence requirements of short capped RNAs by the methyltransferase domain of dengue virus NS5. J Mol Biol. 2007;372:723-36 pubmed
    ..A putative Flavivirus RNA capping pathway is proposed combining the different steps where the NS5MTase domain is involved. ..

More Information

Publications62

  1. Yoffe Y, Zuberek J, Lerer A, Lewdorowicz M, Stepinski J, Altmann M, et al. Binding specificities and potential roles of isoforms of eukaryotic initiation factor 4E in Leishmania. Eukaryot Cell. 2006;5:1969-79 pubmed
    ..None of the isoforms can functionally complement the Saccharomyces cerevisiae eIF4E, indicating that despite their structural conservation, they are considerably diverged. ..
  2. Monecke T, Dickmanns A, Strasser A, Ficner R. Structure analysis of the conserved methyltransferase domain of human trimethylguanosine synthase TGS1. Acta Crystallogr D Biol Crystallogr. 2009;65:332-8 pubmed publisher
    ..These structural data are consistent with the finding that the crystallized fragment of human TGS1 is catalytically inactive, while a fragment that is 17 amino acids longer exhibits activity. ..
  3. Monecke T, Schell S, Dickmanns A, Ficner R. Crystal structure of the RRM domain of poly(A)-specific ribonuclease reveals a novel m(7)G-cap-binding mode. J Mol Biol. 2008;382:827-34 pubmed publisher
    ..The crystal structure also shows a remarkable conformational flexibility of the RRM domain, leading to a perfect exchange of two alpha-helices with an adjacent protein molecule in the crystal lattice. ..
  4. Rutkowska Wlodarczyk I, Stepinski J, Dadlez M, Darzynkiewicz E, Stolarski R, Niedzwiecka A. Structural changes of eIF4E upon binding to the mRNA 5' monomethylguanosine and trimethylguanosine Cap. Biochemistry. 2008;47:2710-20 pubmed publisher
  5. Ziemniak M, Strenkowska M, Kowalska J, Jemielity J. Potential therapeutic applications of RNA cap analogs. Future Med Chem. 2013;5:1141-72 pubmed publisher
    ..Advances achieved to date, challenges, plausible solutions and prospects for the future development of cap analog-based drug design are described. ..
  6. Shaloiko L, Granovsky I, Ivashina T, Ksenzenko V, Shirokov V, Spirin A. Effective non-viral leader for cap-independent translation in a eukaryotic cell-free system. Biotechnol Bioeng. 2004;88:730-9 pubmed
    ..We propose the obelin mRNA leader be used for effective cap-independent translation in eukaryotic cell-free systems, including combined transcription-translation systems with uncontrolled phage polymerase-catalyzed accumulation of mRNA. ..
  7. Niedzwiecka A, Darzynkiewicz E, Stolarski R. Thermodynamics of mRNA 5' cap binding by eukaryotic translation initiation factor eIF4E. Biochemistry. 2004;43:13305-17 pubmed
  8. Tomoo K, Shen X, Okabe K, Nozoe Y, Fukuhara S, Morino S, et al. Structural features of human initiation factor 4E, studied by X-ray crystal analyses and molecular dynamics simulations. J Mol Biol. 2003;328:365-83 pubmed
  9. Mazza C, Segref A, Mattaj I, Cusack S. Large-scale induced fit recognition of an m(7)GpppG cap analogue by the human nuclear cap-binding complex. EMBO J. 2002;21:5548-57 pubmed
    ..Implications for the transfer of capped mRNAs to eIF4E, required for translation initiation, are discussed. ..
  10. Tomoo K, Shen X, Okabe K, Nozoe Y, Fukuhara S, Morino S, et al. Crystal structures of 7-methylguanosine 5'-triphosphate (m(7)GTP)- and P(1)-7-methylguanosine-P(3)-adenosine-5',5'-triphosphate (m(7)GpppA)-bound human full-length eukaryotic initiation factor 4E: biological importance of the C-terminal flexible regi. Biochem J. 2002;362:539-44 pubmed
  11. Gao M, Fritz D, Ford L, Wilusz J. Interaction between a poly(A)-specific ribonuclease and the 5' cap influences mRNA deadenylation rates in vitro. Mol Cell. 2000;5:479-88 pubmed
    ..Third, the addition of cap binding protein eIF4E inhibits deadenylation in vitro. These data provide insights into the early steps of substrate recognition that target an mRNA for degradation. ..
  12. van Duijn L, Kasperaitis M, Ameling C, Voorma H. Additional methylation at the N(2)-position of the cap of 26S Semliki Forest virus late mRNA and initiation of translation. Virus Res. 1986;5:61-6 pubmed
    ..Polysomal 26S mRNA contained less m2,7G- and m2,2,7G-caps than free 26S. The cap analog m2,2,7Gp was slightly less inhibitory than m7Gp in an in vitro translation system...
  13. Nagata T, Suzuki S, Endo R, Shirouzu M, Terada T, Inoue M, et al. The RRM domain of poly(A)-specific ribonuclease has a noncanonical binding site for mRNA cap analog recognition. Nucleic Acids Res. 2008;36:4754-67 pubmed publisher
    ..These unique structural features in PARN RRM reveal a novel cap-binding mode, which is distinct from the nucleotide recognition mode of the canonical RRM domains. ..
  14. Guilligay D, Tarendeau F, Resa Infante P, Coloma R, Crepin T, Sehr P, et al. The structural basis for cap binding by influenza virus polymerase subunit PB2. Nat Struct Mol Biol. 2008;15:500-6 pubmed publisher
    ..These findings clarify the nature of the cap binding site in PB2 and will allow efficient structure-based design of new anti-influenza compounds inhibiting viral transcription. ..
  15. Niedzwiecka A, Marcotrigiano J, Stepinski J, Jankowska Anyszka M, Wyslouch Cieszynska A, Dadlez M, et al. Biophysical studies of eIF4E cap-binding protein: recognition of mRNA 5' cap structure and synthetic fragments of eIF4G and 4E-BP1 proteins. J Mol Biol. 2002;319:615-35 pubmed
    ..Phosphorylation of 4E-BP1 at Ser65 and Thr70 is insufficient to prevent binding to eIF4E. Enhancement of the eIF4E affinity for cap occurs after binding to eIF4G peptides. ..
  16. Mouaikel J, Verheggen C, Bertrand E, Tazi J, Bordonné R. Hypermethylation of the cap structure of both yeast snRNAs and snoRNAs requires a conserved methyltransferase that is localized to the nucleolus. Mol Cell. 2002;9:891-901 pubmed
    ..Consistently, Tgs1p is also localized in the nucleolus. Our results suggest a trafficking pathway in which yeast snRNAs and snoRNAs cycle through the nucleolus to undergo m(7)G cap hypermethylation. ..
  17. Sosnovtsev S, Green K. RNA transcripts derived from a cloned full-length copy of the feline calicivirus genome do not require VpG for infectivity. Virology. 1995;210:383-90 pubmed publisher
  18. Alekhina O, Vassilenko K, Spirin A. Translation of non-capped mRNAs in a eukaryotic cell-free system: acceleration of initiation rate in the course of polysome formation. Nucleic Acids Res. 2007;35:6547-59 pubmed
    ..The eIF4F-mediated circularization of polysomes may be considered as a possible event that leads to the re-initiation switch and the resultant acceleration effect...
  19. Monecke T, Dickmanns A, Ficner R. Structural basis for m7G-cap hypermethylation of small nuclear, small nucleolar and telomerase RNA by the dimethyltransferase TGS1. Nucleic Acids Res. 2009;37:3865-77 pubmed publisher
    ..The crystal structure of the substrate bound methyltransferase domain as well as mutagenesis studies provide insight into the catalytic mechanism of TGS1. ..
  20. Kore A, Shanmugasundaram M, Vlassov A. Synthesis and application of a new 2',3'-isopropylidene guanosine substituted cap analog. Bioorg Med Chem Lett. 2008;18:4828-32 pubmed publisher
    ..The observed increase in the level of protein synthesis is likely resulted as a consequence of exclusively forward capped transcripts and increased cellular stability of the 5'-modified capped mRNA (Poly A). ..
  21. Stachelska Wierzchowska A, Wieczorek Z. Hydrolysis of 5',5'-tri- or tetraphosphate-mRNA 5'-cap analogs promoted by Cu2+ or Zn2+ metal ions. Nucleosides Nucleotides Nucleic Acids. 2011;30:135-48 pubmed publisher
    ..Dependence of the rates of hydrolysis on the catalyst concentration was in some instances not linear, interpreted as evidence for participation of more than one metal ion in the transition complex. ..
  22. Liu W, Jankowska Anyszka M, Piecyk K, Dickson L, Wallace A, Niedzwiecka A, et al. Structural basis for nematode eIF4E binding an m(2,2,7)G-Cap and its implications for translation initiation. Nucleic Acids Res. 2011;39:8820-32 pubmed publisher
    ..These data have implications for the contribution of 5'-UTRs in mRNA translation and the function of different eIF4E isoforms. ..
  23. Chen Y, Su C, Ke M, Jin X, Xu L, Zhang Z, et al. Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2'-O-methylation by nsp16/nsp10 protein complex. PLoS Pathog. 2011;7:e1002294 pubmed publisher
    ..These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs. ..
  24. Khan M, Goss D. Phosphorylation states of translational initiation factors affect mRNA cap binding in wheat. Biochemistry. 2004;43:9092-7 pubmed
    ..Phosphorylation may modulate not only cap-binding activity, but other functions of eukaryotic initiation factors as well. ..
  25. Joshi B, Yan R, Rhoads R. In vitro synthesis of human protein synthesis initiation factor 4 gamma and its localization on 43 and 48 S initiation complexes. J Biol Chem. 1994;269:2048-55 pubmed
    ..This supports a model in which free eIF-4E binds to mRNA followed by binding of the eIF-4E.mRNA complex to a 43 S initiation complex already containing eIF-4 gamma. ..
  26. Ishikawa M, Murai R, Hagiwara H, Hoshino T, Suyama K. Preparation of eukaryotic mRNA having differently methylated adenosine at the 5'-terminus and the effect of the methyl group in translation. Nucleic Acids Symp Ser (Oxf). 2009;:129-30 pubmed publisher
    ..In the case of m(7)G(5')pppApG (plant type) efficiency of translation was lowest. ..
  27. Mitchell S, Walker S, Algire M, Park E, Hinnebusch A, Lorsch J. The 5'-7-methylguanosine cap on eukaryotic mRNAs serves both to stimulate canonical translation initiation and to block an alternative pathway. Mol Cell. 2010;39:950-62 pubmed publisher
  28. Wang Y, Wang J, Ping J, Yu Y, Wang Y, Lian P, et al. Computational studies on the substrate interactions of influenza A virus PB2 subunit. PLoS ONE. 2012;7:e44079 pubmed publisher
    ..We believed that our findings could give an atomic insight into the deeper understanding of the cap recognition and binding mechanism, providing useful information for searching or designing novel drugs against influenza viruses...
  29. Shanmugasundaram M, Charles I, Kore A. Design, synthesis and biological evaluation of dinucleotide mRNA cap analog containing propargyl moiety. Bioorg Med Chem. 2016;24:1204-8 pubmed publisher
    ..1 fold in terms of translational properties. The propargyl cap analog forms a more stable complex with translation initiation factor eIF4E based on the molecular modeling studies. ..
  30. Friedland D, Wooten W, LaVoy J, Hagedorn C, Goss D. A mutant of eukaryotic protein synthesis initiation factor eIF4E(K119A) has an increased binding affinity for both m7G cap analogues and eIF4G peptides. Biochemistry. 2005;44:4546-50 pubmed
    ..Entropic contributions to binding suggesting hydrophobic interactions are larger in the mutant protein and are most likely due to a conformational change. ..
  31. Ghosh P, Park C, Peterson M, Bitterman P, Polunovsky V, Wagner C. Synthesis and evaluation of potential inhibitors of eIF4E cap binding to 7-methyl GTP. Bioorg Med Chem Lett. 2005;15:2177-80 pubmed
    ..5'-H-Phosphonate derivatives in which the 2'- and 3'-riboside hydroxyls were tethered together by an isopropylidene group were shown to be a new class of inhibitors of eIF4E binding to capped mRNA. ..
  32. Kore A, Shanmugasundaram M. Synthesis and biological evaluation of trimethyl-substituted cap analogs. Bioorg Med Chem Lett. 2008;18:880-4 pubmed publisher
    ..The other two variants were also more efficient, generating, approximately 2.2 times (for the [see text] analog) and, approximately 1.6 times (for the m(7)G[5']ppp[5']m(7)G analog) more luciferase function than the conventional cap. ..
  33. Kowalska J, Lewdorowicz M, Zuberek J, Bojarska E, Wojcik J, Cohen L, et al. Synthesis and properties of mRNA cap analogs containing phosphorothioate moiety in 5',5'-triphosphate chain. Nucleosides Nucleotides Nucleic Acids. 2005;24:595-600 pubmed
    ..We present here the results of preliminary studies on their interaction with translation initiation factor eIF4E and enzymatic hydrolysis with human and nematode DcpS scavengers. ..
  34. Grudzien Nogalska E, Stepinski J, Jemielity J, Zuberek J, Stolarski R, Rhoads R, et al. Synthesis of anti-reverse cap analogs (ARCAs) and their applications in mRNA translation and stability. Methods Enzymol. 2007;431:203-27 pubmed
    ..In this chapter, we describe the synthesis of representative ARCAs and their biophysical and biochemical characterization, with emphasis on practical applications in mRNA translation. ..
  35. Peyrane F, Selisko B, Decroly E, Vasseur J, Benarroch D, Canard B, et al. High-yield production of short GpppA- and 7MeGpppA-capped RNAs and HPLC-monitoring of methyltransfer reactions at the guanine-N7 and adenosine-2'O positions. Nucleic Acids Res. 2007;35:e26 pubmed publisher
    ..Additionally, the produced capped RNAs may serve in biochemical, inhibition and structural studies involving a variety of eukaryotic and viral methyltransferases and guanylyltransferases...
  36. Kaiser C, Dobrikova E, Bradrick S, Shveygert M, Herbert J, Gromeier M. Activation of cap-independent translation by variant eukaryotic initiation factor 4G in vivo. RNA. 2008;14:2170-82 pubmed publisher
    ..Our work demonstrates that variant translation initiation factors enable unconventional translation initiation at mRNA subsets with distinct structural features. ..
  37. Stepinski J, Zuberek J, Jemielity J, Kalek M, Stolarski R, Darzynkiewicz E. Novel dinucleoside 5',5'-triphosphate cap analogues. Synthesis and affinity for murine translation factor eIF4E. Nucleosides Nucleotides Nucleic Acids. 2005;24:629-33 pubmed
    ..The binding affinity of the new cap analogues for murine eIF4E(28-217) were determined spectroscopically showing the highest association constant for the analogue that contains formycin A. ..
  38. Roberts A, Lewis A, Jopling C. miR-122 activates hepatitis C virus translation by a specialized mechanism requiring particular RNA components. Nucleic Acids Res. 2011;39:7716-29 pubmed publisher
    ..This study provides an important insight into the requirements for the miR-122-HCV interaction, and the broader consequences of miRNAs binding to 5'-UTR sites. ..
  39. Tomoo K, Matsushita Y, Fujisaki H, Abiko F, Shen X, Taniguchi T, et al. Structural basis for mRNA Cap-Binding regulation of eukaryotic initiation factor 4E by 4E-binding protein, studied by spectroscopic, X-ray crystal structural, and molecular dynamics simulation methods. Biochim Biophys Acta. 2005;1753:191-208 pubmed
    ..These results provide the structural basis for the mRNA cap-binding regulation of eIF4E by 4E-BP. ..
  40. Lin W, Wadlington N, Chen L, Zhuang X, Brorson J, Kang U. Loss of PINK1 attenuates HIF-1? induction by preventing 4E-BP1-dependent switch in protein translation under hypoxia. J Neurosci. 2014;34:3079-89 pubmed publisher
  41. Wypijewska A, Bojarska E, Stepinski J, Jankowska Anyszka M, Jemielity J, Davis R, et al. Structural requirements for Caenorhabditis elegans DcpS substrates based on fluorescence and HPLC enzyme kinetic studies. FEBS J. 2010;277:3003-13 pubmed publisher
    ..Moreover, although C. elegans DcpS accommodates bulkier groups in the N7 position (ethyl or benzyl) of the cap, both 2'-O- and 3'-O-methylations of 7-methylguanosine result in a reduction in hydrolysis by two orders of magnitude. ..
  42. Zuberek J, Kubacka D, Jablonowska A, Jemielity J, Stepinski J, Sonenberg N, et al. Weak binding affinity of human 4EHP for mRNA cap analogs. RNA. 2007;13:691-7 pubmed
    ..We show that 4EHP binds cap analogs m(7)GpppG and m(7)GTP with 30 and 100 lower affinity than eIF4E. Thus, 4EHP cannot compete with eIF4E for binding to the cap structure of most mRNAs. ..
  43. Grudzien Nogalska E, Jemielity J, Kowalska J, Darzynkiewicz E, Rhoads R. Phosphorothioate cap analogs stabilize mRNA and increase translational efficiency in mammalian cells. RNA. 2007;13:1745-55 pubmed
    ..The greater yield of protein due to combining higher translational efficiency with longer t (1/2) of mRNA should benefit applications that utilize RNA transfection such as protein production, anti-cancer immunization, and gene therapy. ..
  44. Severin C, Rocha de Moura T, Liu Y, Li K, Zheng X, Luo M. The cap-binding site of influenza virus protein PB2 as a drug target. Acta Crystallogr D Struct Biol. 2016;72:245-53 pubmed publisher
    ..Analysis of the new H1N1 structures and comparisons with other structures provide new insights into the design of small-molecule inhibitors that will be effective against multiple strains of both type A and type B influenza viruses. ..
  45. Yoffe Y, Léger M, Zinoviev A, Zuberek J, Darzynkiewicz E, Wagner G, et al. Evolutionary changes in the Leishmania eIF4F complex involve variations in the eIF4E-eIF4G interactions. Nucleic Acids Res. 2009;37:3243-53 pubmed publisher
    ..In view of these diversities, the characterization of the parasite eIF4E-eIF4G interaction may not only serve as a novel target for inhibiting Leishmaniasis but also provide important insight for future drug discovery. ..
  46. Nishimura K, Sakuma A, Yamashita T, Hirokawa G, Imataka H, Kashiwagi K, et al. Minor contribution of an internal ribosome entry site in the 5'-UTR of ornithine decarboxylase mRNA on its translation. Biochem Biophys Res Commun. 2007;364:124-30 pubmed
    ..Rapamycin inhibited ODC synthesis by 40-50% at both the G1/S boundary and the G2/M phase. These results indicate that an IRES in the 5'-UTR of ODC mRNA does not function effectively. ..
  47. Moreno P, Wenska M, Lundin K, Wrange O, Stromberg R, Smith C. A synthetic snRNA m3G-CAP enhances nuclear delivery of exogenous proteins and nucleic acids. Nucleic Acids Res. 2009;37:1925-35 pubmed publisher
    ..The synthetic capping of oligos interfering with splicing may have immediate clinical applications. ..
  48. Degen W, Aarssen Y, Pruijn G, Utz P, van Venrooij W. The fate of U1 snRNP during anti-Fas induced apoptosis: specific cleavage of the U1 snRNA molecule. Cell Death Differ. 2000;7:70-9 pubmed
  49. Dong H, Fink K, Zust R, Lim S, Qin C, Shi P. Flavivirus RNA methylation. J Gen Virol. 2014;95:763-78 pubmed publisher
    ..This concept has recently been proved with Japanese encephalitis virus and dengue virus. The findings obtained with flavivirus should be applicable to other RNA viruses. ..
  50. Wypijewska Del Nogal A, Surleac M, Kowalska J, Lukaszewicz M, Jemielity J, Bisaillon M, et al. Analysis of decapping scavenger cap complex using modified cap analogs reveals molecular determinants for efficient cap binding. FEBS J. 2013;280:6508-27 pubmed publisher
    ..Finally, the comparison of CeDcpS with its well known human homolog provides general insights into DcpS-cap interactions. ..
  51. Qi X, Lan S, Wang W, Schelde L, Dong H, Wallat G, et al. Cap binding and immune evasion revealed by Lassa nucleoprotein structure. Nature. 2010;468:779-83 pubmed publisher
    ..These findings provide great potential for vaccine and drug development. ..
  52. Andreev D, Dmitriev S, Terenin I, Prassolov V, Merrick W, Shatsky I. Differential contribution of the m7G-cap to the 5' end-dependent translation initiation of mammalian mRNAs. Nucleic Acids Res. 2009;37:6135-47 pubmed publisher
    ..Thus, it is not mandatory to invoke the IRES hypothesis, at least for some mRNAs, to explain their preferential translation when eIF4E is partially inactivated. ..
  53. Darzynkiewicz Z, Bojarska E, Stepinski J, Jemielity J, Jankowska Anyszka M, Davis R, et al. Affinity of dinucleotide cap analogues for human decapping scavenger (hDcpS). Nucleosides Nucleotides Nucleic Acids. 2007;26:1349-52 pubmed
    ..Cap analogues containing pyrimidine base instead of guanine or diphosphate chain are resistant to hydrolysis catalyzed by human scavenger. Contrary to the other enzymes of HIT family, hDcpS activity is not stimulated by Mg(2+). ..