rna caps


Summary: Nucleic acid structures found on the 5' end of eukaryotic cellular and viral messenger RNA and some heterogeneous nuclear RNAs. These structures, which are positively charged, protect the above specified RNAs at their termini against attack by phosphatases and other nucleases and promote mRNA function at the level of initiation of translation. Analogs of the RNA caps (RNA CAP ANALOGS), which lack the positive charge, inhibit the initiation of protein synthesis.

Top Publications

  1. de la Peña M, Kyrieleis O, Cusack S. Structural insights into the mechanism and evolution of the vaccinia virus mRNA cap N7 methyl-transferase. EMBO J. 2007;26:4913-25 pubmed
  2. Tritschler F, Braun J, Motz C, Igreja C, Haas G, Truffault V, et al. DCP1 forms asymmetric trimers to assemble into active mRNA decapping complexes in metazoa. Proc Natl Acad Sci U S A. 2009;106:21591-6 pubmed publisher
    ..Our results reveal an unexpected connectivity and complexity of the mRNA decapping network in multicellular eukaryotes, which likely enhances opportunities for regulating mRNA degradation. ..
  3. Cao Q, Padmanabhan K, Richter J. Pumilio 2 controls translation by competing with eIF4E for 7-methyl guanosine cap recognition. RNA. 2010;16:221-7 pubmed publisher
    ..Thus, in addition to its suggested role in regulating poly(A) tail length and mRNA stability, our results suggest that vertebrate Pumilio can repress translation by blocking the assembly of the essential initiation complex on the cap...
  4. Hu W, Sweet T, Chamnongpol S, Baker K, Coller J. Co-translational mRNA decay in Saccharomyces cerevisiae. Nature. 2009;461:225-9 pubmed publisher
    ..The data indicate that dissociation of ribosomes from mRNA is not a prerequisite for decay and we suggest that the 5'-3' polarity of mRNA degradation has evolved to ensure that the last translocating ribosome can complete translation...
  5. Lahudkar S, Shukla A, Bajwa P, Durairaj G, Stanojevic N, Bhaumik S. The mRNA cap-binding complex stimulates the formation of pre-initiation complex at the promoter via its interaction with Mot1p in vivo. Nucleic Acids Res. 2011;39:2188-209 pubmed publisher
  6. Fischer P. Cap in hand: targeting eIF4E. Cell Cycle. 2009;8:2535-41 pubmed
    ..The emerging understanding of the functions, regulation, and structural biology of eIF4E now makes possible the pharmacological targeting of this key translation initiation factor. ..
  7. Issur M, Picard Jean F, Bisaillon M. The RNA capping machinery as an anti-infective target. Wiley Interdiscip Rev RNA. 2011;2:184-92 pubmed publisher
    ..Here, we examine various strategies that have been developed to inhibit microbial enzymes involved in the synthesis of the RNA cap structure, emphasizing the challenges remaining to design potent and selective drugs. ..
  8. Boivin S, Cusack S, Ruigrok R, Hart D. Influenza A virus polymerase: structural insights into replication and host adaptation mechanisms. J Biol Chem. 2010;285:28411-7 pubmed publisher
    ..Recent proteomic and genome-wide interactome and RNA interference screens have suggested the identities of some of these potential regulators of polymerase function. ..
  9. Nechaev S, Fargo D, dos Santos G, Liu L, Gao Y, Adelman K. Global analysis of short RNAs reveals widespread promoter-proximal stalling and arrest of Pol II in Drosophila. Science. 2010;327:335-8 pubmed publisher
    ..These results indicate that the intrinsic efficiency of early elongation can greatly affect gene expression. ..

More Information


  1. Gowda M, Nunes C, Sailsbery J, Xue M, Chen F, Nelson C, et al. Genome-wide characterization of methylguanosine-capped and polyadenylated small RNAs in the rice blast fungus Magnaporthe oryzae. Nucleic Acids Res. 2010;38:7558-69 pubmed publisher
    ..CPA-sRNAs were independently confirmed using a high affinity variant of eIF-4E to capture 5'-methylguanosine-capped RNA followed by 3'-RACE sequencing. These results expand the repertoire of small RNAs in filamentous fungi. ..
  2. Folkers M, Delker D, Maxwell C, Nelson C, Schwartz J, Nix D, et al. ENCODE tiling array analysis identifies differentially expressed annotated and novel 5' capped RNAs in hepatitis C infected liver. PLoS ONE. 2011;6:e14697 pubmed publisher
  3. Frank F, Fabian M, Stepinski J, Jemielity J, Darzynkiewicz E, Sonenberg N, et al. Structural analysis of 5'-mRNA-cap interactions with the human AGO2 MID domain. EMBO Rep. 2011;12:415-20 pubmed publisher
    ..Additionally, in vitro pull-down experiments with full-length hAGO2 indicate that the interaction with cap analogues is nonspecific. ..
  4. Wu M, Nilsson P, Henriksson N, Niedzwiecka A, Lim M, Cheng Z, et al. Structural basis of m(7)GpppG binding to poly(A)-specific ribonuclease. Structure. 2009;17:276-86 pubmed publisher
  5. Jones B, Quang Dang D, Oku Y, Gross J. A kinetic assay to monitor RNA decapping under single- turnover conditions. Methods Enzymol. 2008;448:23-40 pubmed publisher
  6. Franks T, Lykke Andersen J. The control of mRNA decapping and P-body formation. Mol Cell. 2008;32:605-15 pubmed publisher
    ..Here, we discuss the regulation of decapping machinery recruitment to specific mRNPs and how their assembly into PBs is governed by the relative rates of translational repression, mRNP multimerization, and mRNA decay. ..
  7. Graber T, Holcik M. Cap-independent regulation of gene expression in apoptosis. Mol Biosyst. 2007;3:825-34 pubmed
    ..In addition, recent advances towards our understanding of the physiological role and mechanism of IRES-mediated translation in the context of cell stress-induced apoptosis and human disease will be examined. ..
  8. Li J, Rahmeh A, Morelli M, Whelan S. A conserved motif in region v of the large polymerase proteins of nonsegmented negative-sense RNA viruses that is essential for mRNA capping. J Virol. 2008;82:775-84 pubmed
  9. Pilkington G, Parker R. Pat1 contains distinct functional domains that promote P-body assembly and activation of decapping. Mol Cell Biol. 2008;28:1298-312 pubmed
    ..These results indicate that Pat1 is an RNA binding protein and a multidomain protein that functions at multiple stages in the process of translation repression and mRNA decapping...
  10. Cheng E, Mir M. Signatures of host mRNA 5' terminus for efficient hantavirus cap snatching. J Virol. 2012;86:10173-85 pubmed publisher
    ..Our results suggest that efficiency of an mRNA to donate caps for viral mRNA synthesis is primarily regulated at the translational level. ..
  11. Mukherjee C, Patil D, Kennedy B, Bakthavachalu B, Bundschuh R, Schoenberg D. Identification of cytoplasmic capping targets reveals a role for cap homeostasis in translation and mRNA stability. Cell Rep. 2012;2:674-84 pubmed publisher
    ..These findings identify a cyclical process of decapping and recapping that we term cap homeostasis. ..
  12. Sonenberg N. eIF4E, the mRNA cap-binding protein: from basic discovery to translational research. Biochem Cell Biol. 2008;86:178-83 pubmed publisher
    ..In this article I describe the discovery of eIF4E, its mechanism of action in translation initiation, and its role in the control of cancer and innate immunity. ..
  13. Michlewski G, Sanford J, Caceres J. The splicing factor SF2/ASF regulates translation initiation by enhancing phosphorylation of 4E-BP1. Mol Cell. 2008;30:179-89 pubmed publisher
    ..Taken together, these data suggest a novel mechanism for the activation of translation initiation of a subset of mRNAs bound by the shuttling protein SF2/ASF. ..
  14. Jiao X, Chang J, Kilic T, Tong L, Kiledjian M. A mammalian pre-mRNA 5' end capping quality control mechanism and an unexpected link of capping to pre-mRNA processing. Mol Cell. 2013;50:104-15 pubmed publisher
  15. Habjan M, Hubel P, Lacerda L, Benda C, Holze C, Eberl C, et al. Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA. PLoS Pathog. 2013;9:e1003663 pubmed publisher
  16. Lidschreiber M, Leike K, Cramer P. Cap completion and C-terminal repeat domain kinase recruitment underlie the initiation-elongation transition of RNA polymerase II. Mol Cell Biol. 2013;33:3805-16 pubmed publisher
    ..Abd1 and CBC are important for recruitment of the kinases Ctk1 and Bur1, which promote elongation and capping enzyme release. These results suggest that cap completion stimulates productive Pol II elongation. ..
  17. Osborne M, Volpon L, Kornblatt J, Culjkovic Kraljacic B, Baguet A, Borden K. eIF4E3 acts as a tumor suppressor by utilizing an atypical mode of methyl-7-guanosine cap recognition. Proc Natl Acad Sci U S A. 2013;110:3877-82 pubmed publisher
    ..Taken together, there is more structural plasticity in cap recognition than previously thought, and this is physiologically relevant. ..
  18. Braunstein S, Karpisheva K, Pola C, Goldberg J, Hochman T, Yee H, et al. A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer. Mol Cell. 2007;28:501-12 pubmed
    ..The switch from cap-dependent to cap-independent mRNA translation facilitates tumor angiogenesis and hypoxia responses in animal models. ..
  19. Cooke A, Prigge A, Wickens M. Translational repression by deadenylases. J Biol Chem. 2010;285:28506-13 pubmed publisher
    ..The deadenylation-independent repression requires a 5' cap structure on the mRNA; however, deadenylation does not. We suggest that mere recruitment of CAF1 is sufficient for repression, independent of deadenylation. ..
  20. Dong H, Chang D, Xie X, Toh Y, Chung K, Zou G, et al. Biochemical and genetic characterization of dengue virus methyltransferase. Virology. 2010;405:568-78 pubmed publisher
  21. Reguera J, Weber F, Cusack S. Bunyaviridae RNA polymerases (L-protein) have an N-terminal, influenza-like endonuclease domain, essential for viral cap-dependent transcription. PLoS Pathog. 2010;6:e1001101 pubmed publisher
  22. Nicholson B, White K. 3' Cap-independent translation enhancers of positive-strand RNA plant viruses. Curr Opin Virol. 2011;1:373-80 pubmed publisher
  23. Ghosh A, Lima C. Enzymology of RNA cap synthesis. Wiley Interdiscip Rev RNA. 2010;1:152-72 pubmed publisher
    ..Although mRNA capping is conserved among viruses and eukaryotes, some viruses have adopted strategies for capping mRNA that are distinct from the cellular mRNA capping pathway. ..
  24. Topisirovic I, Svitkin Y, Sonenberg N, Shatkin A. Cap and cap-binding proteins in the control of gene expression. Wiley Interdiscip Rev RNA. 2011;2:277-98 pubmed publisher
    ..We also describe emerging regulatory pathways that control mRNA capping and cap-binding proteins in the cell. ..
  25. Szretter K, Daniels B, Cho H, Gainey M, Yokoyama W, Gale M, et al. 2'-O methylation of the viral mRNA cap by West Nile virus evades ifit1-dependent and -independent mechanisms of host restriction in vivo. PLoS Pathog. 2012;8:e1002698 pubmed publisher
  26. Decroly E, Ferron F, Lescar J, Canard B. Conventional and unconventional mechanisms for capping viral mRNA. Nat Rev Microbiol. 2011;10:51-65 pubmed publisher
    ..Viral RNA caps can be stolen from cellular mRNAs or synthesized using either a host- or virus-encoded capping apparatus, and ..
  27. Shimakami T, Yamane D, Jangra R, Kempf B, Spaniel C, Barton D, et al. Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. Proc Natl Acad Sci U S A. 2012;109:941-6 pubmed publisher
    ..miR-122 thus acts in an unconventional fashion to stabilize HCV RNA and slow its decay, expanding the repertoire of mechanisms by which miRNAs modulate gene expression. ..
  28. Chang J, Schwer B, Shuman S. Mutational analyses of trimethylguanosine synthase (Tgs1) and Mud2: proteins implicated in pre-mRNA splicing. RNA. 2010;16:1018-31 pubmed publisher
    ..Mud2 mutational effects in the swm2Delta background paralleled those for mud1Delta. The requirements for Mud2 function are apparently more stringent when yeast cells lack TMG caps than when they lack Mud1 or Swm2. ..
  29. Worch R, Jankowska Anyszka M, Niedzwiecka A, Stepinski J, Mazza C, Darzynkiewicz E, et al. Diverse role of three tyrosines in binding of the RNA 5' cap to the human nuclear cap binding complex. J Mol Biol. 2009;385:618-27 pubmed publisher
    ..The resulting kinetic model of the association between the capped RNA and CBC, based on the experimental data and quantum calculations, is discussed with respect to the "CBC-to-eukaryotic initiation factor 4E handoff" of mRNA. ..
  30. Li J, Rahmeh A, Brusic V, Whelan S. Opposing effects of inhibiting cap addition and cap methylation on polyadenylation during vesicular stomatitis virus mRNA synthesis. J Virol. 2009;83:1930-40 pubmed publisher
    ..This work reveals that inhibiting cap addition and cap methylation have opposing effects on polyadenylation during VSV mRNA synthesis and provides evidence in support of a link between correct 5' cap formation and 3' polyadenylation...
  31. Cole M, Cowling V. Specific regulation of mRNA cap methylation by the c-Myc and E2F1 transcription factors. Oncogene. 2009;28:1169-75 pubmed publisher
    ..c-Myc-induced cap methylation is greater than transcriptional induction for the majority of its target genes, indicating that this is a major mechanism by which Myc regulates gene expression. ..
  32. Kinch L, Grishin N. The human Ago2 MC region does not contain an eIF4E-like mRNA cap binding motif. Biol Direct. 2009;4:2 pubmed publisher
    ..Mapping of the MC sequence to the mid domain structure reveals Ago2 aromatics that are incompatible with eIF4E-like mRNA cap-binding, yet display some limited local structure similarities that cause the chance sequence match to eIF4E. ..
  33. Kaye N, Emmett K, Merrick W, Jankowsky E. Intrinsic RNA binding by the eukaryotic initiation factor 4F depends on a minimal RNA length but not on the m7G cap. J Biol Chem. 2009;284:17742-50 pubmed publisher
    ..The nonetheless essential m7G cap may either function at steps subsequent to eIF4F-RNA binding, or other factors facilitate preferential binding of eIF4F to the m7G cap. ..
  34. Van Der Kelen K, Beyaert R, Inze D, De Veylder L. Translational control of eukaryotic gene expression. Crit Rev Biochem Mol Biol. 2009;44:143-68 pubmed publisher
  35. Goette M, Stumpe M, Ficner R, Grubmuller H. Molecular determinants of snurportin 1 ligand affinity and structural response upon binding. Biophys J. 2009;97:581-9 pubmed publisher
    ..In particular, desolvation of the ligand is revealed as the key-step in binding to snurportin 1. These findings suggest that the binding of m(3)G-capped RNA is mainly driven by the enhanced water entropy gain of the solvation shell. ..
  36. Chowdhury A, Tharun S. Activation of decapping involves binding of the mRNA and facilitation of the post-binding steps by the Lsm1-7-Pat1 complex. RNA. 2009;15:1837-48 pubmed publisher
    ..Consistent with these ideas, the lsm1-9, 14 allele generated by combining the mutations of lsm1-9 and lsm1-14 alleles had almost fully lost the RNA binding activity of the complex and behaved like the lsm1-8 mutant. ..
  37. Selisko B, Peyrane F, Canard B, Alvarez K, Decroly E. Biochemical characterization of the (nucleoside-2'O)-methyltransferase activity of dengue virus protein NS5 using purified capped RNA oligonucleotides (7Me)GpppAC(n) and GpppAC(n). J Gen Virol. 2010;91:112-21 pubmed publisher
    ..34 microM) and sinefungin (IC(50) 0.63 microM), demonstrating that the assay is sufficiently sensitive to conduct inhibitor screening and characterization assays. ..
  38. Bajak E, Hagedorn C. Efficient 5' cap-dependent RNA purification : use in identifying and studying subsets of RNA. Methods Mol Biol. 2008;419:147-60 pubmed publisher
    ..The length of the 3' poly(A) ends can be defined using a rapid polymerase chain reaction (PCR)- based approach. ..
  39. Cowling V. Regulation of mRNA cap methylation. Biochem J. 2009;425:295-302 pubmed publisher
    ..The present review discusses how the 7-methylguanosine cap is synthesized by cellular enzymes, the impact that the 7-methylguanosine cap has on biological processes, and how the mRNA cap methylation reaction is regulated. ..
  40. Chuang T, Chang W, Lee K, Tarn W. The RNA-binding protein Y14 inhibits mRNA decapping and modulates processing body formation. Mol Biol Cell. 2013;24:1-13 pubmed publisher
  41. Decroly E, Imbert I, Coutard B, Bouvet M, Selisko B, Alvarez K, et al. Coronavirus nonstructural protein 16 is a cap-0 binding enzyme possessing (nucleoside-2'O)-methyltransferase activity. J Virol. 2008;82:8071-84 pubmed publisher
  42. Ogino T, Banerjee A. Formation of guanosine(5')tetraphospho(5')adenosine cap structure by an unconventional mRNA capping enzyme of vesicular stomatitis virus. J Virol. 2008;82:7729-34 pubmed publisher
    ..Interestingly, GppppA-capped and polyadenylated full-length mRNAs were also found to be synthesized by an in vitro transcription system with the native VSV RNP...
  43. 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. ..
  44. Lindqvist L, Imataka H, Pelletier J. Cap-dependent eukaryotic initiation factor-mRNA interactions probed by cross-linking. RNA. 2008;14:960-9 pubmed publisher
    ..Using this approach, we demonstrate interactions between eIF4G, eIF4H, and eIF3 subunits with the mRNA during the cap recognition process. ..
  45. Glover Cutter K, Kim S, Espinosa J, Bentley D. RNA polymerase II pauses and associates with pre-mRNA processing factors at both ends of genes. Nat Struct Mol Biol. 2008;15:71-8 pubmed
    ..We propose a dual-pausing model wherein elongation arrests near the transcription start site and in the 3' flank to allow co-transcriptional processing by factors recruited to the pol II ternary complex. ..
  46. Cole M, Cowling V. Transcription-independent functions of MYC: regulation of translation and DNA replication. Nat Rev Mol Cell Biol. 2008;9:810-5 pubmed publisher
    ..Recently, MYC was shown to control protein expression through mRNA translation and to directly regulate DNA replication, thus initiating exciting new areas of oncogene research. ..
  47. Geiss B, Thompson A, Andrews A, Sons R, Gari H, Keenan S, et al. Analysis of flavivirus NS5 methyltransferase cap binding. J Mol Biol. 2009;385:1643-54 pubmed publisher
    ..A detailed model of how the flavivirus MTase protein binds RNA cap structures is presented. ..
  48. Viladevall L, St Amour C, Rosebrock A, Schneider S, Zhang C, Allen J, et al. TFIIH and P-TEFb coordinate transcription with capping enzyme recruitment at specific genes in fission yeast. Mol Cell. 2009;33:738-51 pubmed publisher
    ..In vitro, phosphorylation of the CTD by Mcs6 stimulates subsequent phosphorylation by Cdk9. We propose that TFIIH primes the CTD and promotes recruitment of P-TEFb/Pcm1, serving to couple elongation and capping of select pre-mRNAs. ..
  49. Li Y, Song M, Kiledjian M. Differential utilization of decapping enzymes in mammalian mRNA decay pathways. RNA. 2011;17:419-28 pubmed publisher
    ..These data demonstrate that the two distinct decapping enzymes can uniquely function in specific mRNA decay processes in mammalian cells. ..
  50. Rahmeh A, Li J, Kranzusch P, Whelan S. Ribose 2'-O methylation of the vesicular stomatitis virus mRNA cap precedes and facilitates subsequent guanine-N-7 methylation by the large polymerase protein. J Virol. 2009;83:11043-50 pubmed publisher
    ..We propose a model of regulation of the activity of the C terminus of L protein in 2'-O and G-N-7 methylation of the cap structure. ..
  51. Issur M, Geiss B, Bougie I, Picard Jean F, Despins S, Mayette J, et al. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009;15:2340-50 pubmed publisher
    ..Our study provides biochemical evidence that flaviviruses encode a complete RNA capping machinery. ..
  52. Bouvet M, Debarnot C, Imbert I, Selisko B, Snijder E, Canard B, et al. In vitro reconstitution of SARS-coronavirus mRNA cap methylation. PLoS Pathog. 2010;6:e1000863 pubmed publisher
  53. Haas G, Braun J, Igreja C, Tritschler F, Nishihara T, Izaurralde E. HPat provides a link between deadenylation and decapping in metazoa. J Cell Biol. 2010;189:289-302 pubmed publisher