nuclear cap binding protein complex


Summary: A heterodimeric protein complex of RNA cap-binding proteins, which binds with high affinity to the 5' MRNA CAP STRUCTURE in the CELL NUCLEUS. The complex contains two subunits, one of 80-kDa molecular weight and another of 20-kDa molecular weight.

Top Publications

  1. Svitkin Y, Pause A, Haghighat A, Pyronnet S, Witherell G, Belsham G, et al. The requirement for eukaryotic initiation factor 4A (elF4A) in translation is in direct proportion to the degree of mRNA 5' secondary structure. RNA. 2001;7:382-94 pubmed
    ..Finally, the elF4A mutant forms a more stable complex with elF4G, as compared to the wild-type elF4A, thus explaining the mechanism by which substoichiometric amounts of mutant elF4A inhibit translation. ..
  2. Ma X, Yoon S, Richardson C, Jülich K, Blenis J. SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs. Cell. 2008;133:303-13 pubmed publisher
    ..Thus, SKAR-mediated recruitment of activated S6K1 to newly processed mRNPs serves as a conduit between mTOR checkpoint signaling and the pioneer round of translation when cells exist in conditions supportive of protein synthesis. ..
  3. Gruber J, Zatechka D, Sabin L, Yong J, Lum J, Kong M, et al. Ars2 links the nuclear cap-binding complex to RNA interference and cell proliferation. Cell. 2009;138:328-39 pubmed publisher
    ..These findings provide evidence for a role for Ars2 in RNA interference regulation during cell proliferation. ..
  4. Cheng H, Dufu K, Lee C, Hsu J, Dias A, Reed R. Human mRNA export machinery recruited to the 5' end of mRNA. Cell. 2006;127:1389-400 pubmed
    ..As a consequence, the mRNA would be exported in a 5' to 3' direction through the nuclear pore, as observed in early electron micrographs of giant Balbiani ring mRNPs. ..
  5. Balatsos N, Nilsson P, Mazza C, Cusack S, Virtanen A. Inhibition of mRNA deadenylation by the nuclear cap binding complex (CBC). J Biol Chem. 2006;281:4517-22 pubmed
    ..Association of CBC with PARN might have importance in the regulated recruitment of PARN to the nonsense-mediated decay pathway during the pioneer round of translation. ..
  6. Worch R, Niedzwiecka A, Stepinski J, Mazza C, Jankowska Anyszka M, Darzynkiewicz E, et al. Specificity of recognition of mRNA 5' cap by human nuclear cap-binding complex. RNA. 2005;11:1355-63 pubmed
    ..Differences in the cap binding of CBC compared with the eukaryotic translation initiation factor 4E (eIF4E) are analyzed and discussed regarding replacement of CBC by eIF4E. ..
  7. 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. ..
  8. Chiu S, Lejeune F, Ranganathan A, Maquat L. The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex. Genes Dev. 2004;18:745-54 pubmed
    ..Polysome profiles indicate that CBP80-bound mRNAs are translated less efficiently than their eIF4E-bound counterparts. ..
  9. Calero G, Wilson K, Ly T, Rios Steiner J, Clardy J, Cerione R. Structural basis of m7GpppG binding to the nuclear cap-binding protein complex. Nat Struct Biol. 2002;9:912-7 pubmed

More Information


  1. Sabin L, Zhou R, Gruber J, Lukinova N, Bambina S, Berman A, et al. Ars2 regulates both miRNA- and siRNA- dependent silencing and suppresses RNA virus infection in Drosophila. Cell. 2009;138:340-51 pubmed publisher
    ..The identification of Ars2 as a player in these small RNA pathways provides new insight into the biogenesis of small RNAs that may be extended to other systems. ..
  2. Laubinger S, Sachsenberg T, Zeller G, Busch W, Lohmann J, Rätsch G, et al. Dual roles of the nuclear cap-binding complex and SERRATE in pre-mRNA splicing and microRNA processing in Arabidopsis thaliana. Proc Natl Acad Sci U S A. 2008;105:8795-800 pubmed publisher
    ..Taken together, our results uncover dual roles in splicing and miRNA processing that distinguish SE and the cap-binding complex from specialized miRNA processing factors such as DCL1 and HYL1. ..
  3. Nojima T, Hirose T, Kimura H, Hagiwara M. The interaction between cap-binding complex and RNA export factor is required for intronless mRNA export. J Biol Chem. 2007;282:15645-51 pubmed publisher
    ..The export of Cy3-labeled intronless beta-globin mRNA from nuclei of HeLa cells was enhanced by co-injection of CBP20 and REF. Thus, REF recruited by CBP20 may play a stimulatory role to export the capped intronless mRNAs...
  4. Ibrahimo S, Holmes L, Ashe M. Regulation of translation initiation by the yeast eIF4E binding proteins is required for the pseudohyphal response. Yeast. 2006;23:1075-88 pubmed
    ..Therefore, this work supports a model where the yeast 4E-BPs are acting on specific mRNAs to facilitate a defined proliferative response to environmental stress in yeast. ..
  5. Morris C, Wittmann J, Jack H, Jalinot P. Human INT6/eIF3e is required for nonsense-mediated mRNA decay. EMBO Rep. 2007;8:596-602 pubmed
    ..From these observations, we propose that INT6, in association with eIF3, is involved in routing specific mRNAs for degradation...
  6. Kennedy K, Ostrakhovitch E, Sandiford S, Dayarathna T, Xie X, Waese E, et al. Mammalian numb-interacting protein 1/dual oxidase maturation factor 1 directs neuronal fate in stem cells. J Biol Chem. 2010;285:17974-85 pubmed publisher
  7. Ryu I, Kim Y. Translation initiation mediated by nuclear cap-binding protein complex. BMB Rep. 2017;50:186-193 pubmed
    ..In this review, we summarize and compare the molecular features of CT and ET with a focus on the emerging roles of CT in translation. [BMB Reports 2017; 50(4): 186-193]. ..
  8. 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. ..
  9. Mazza C, Segref A, Mattaj I, Cusack S. Co-crystallization of the human nuclear cap-binding complex with a m7GpppG cap analogue using protein engineering. Acta Crystallogr D Biol Crystallogr. 2002;58:2194-7 pubmed
    ..3 A resolution. In both forms, strong extra electron density is observed for the cap analogue and for the N- and C-terminal extensions of CBP20 which was absent or disordered in all previous structures. ..
  10. Ostrakhovitch E, Li S. NIP1/DUOXA1 expression in epithelial breast cancer cells: regulation of cell adhesion and actin dynamics. Breast Cancer Res Treat. 2010;119:773-86 pubmed publisher
    ..Our data also demonstrate that DUOXA1 transient overexpression affected the cell-cell adhesion by modulating the actin cytoskeleton, and sensitized cells to doxorubicin. ..
  11. Lewis J, Gorlich D, Mattaj I. A yeast cap binding protein complex (yCBC) acts at an early step in pre-mRNA splicing. Nucleic Acids Res. 1996;24:3332-6 pubmed
    ..These results, together with other data, suggest that CBCs play a highly conserved role in the recognition of pre-mRNA substrates at an early step in the splicing process. ..
  12. Michon T, Estevez Y, Walter J, German Retana S, Le Gall O. The potyviral virus genome-linked protein VPg forms a ternary complex with the eukaryotic initiation factors eIF4E and eIF4G and reduces eIF4E affinity for a mRNA cap analogue. FEBS J. 2006;273:1312-22 pubmed
    ..The strength of interaction between eIF4E and pep4G, the eIF4E-binding domain on eIF4G, was increased significantly by VPg. Taken together these quantitative data show that VPg is an efficient modulator of eIF4E biochemical functions. ..
  13. Matsuda D, Hosoda N, Kim Y, Maquat L. Failsafe nonsense-mediated mRNA decay does not detectably target eIF4E-bound mRNA. Nat Struct Mol Biol. 2007;14:974-9 pubmed
    ..Our studies, including analyses of factor dependence, reveal important shared features of the two mammalian-cell NMD pathways as well as fundamental differences between NMD in mammals and Saccharomyces cerevisiae. ..
  14. Tatham M, Jaffray E, Vaughan O, Desterro J, Botting C, Naismith J, et al. Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. J Biol Chem. 2001;276:35368-74 pubmed
    ..The ability to form polymeric chains is not shared by SUMO-1, and although all SUMO species use the same conjugation machinery, modification by SUMO-1 and SUMO-2/-3 may have distinct functional consequences. ..
  15. Kim K, Cho H, Choi K, Kim J, Kim B, Ko Y, et al. A new MIF4G domain-containing protein, CTIF, directs nuclear cap-binding protein CBP80/20-dependent translation. Genes Dev. 2009;23:2033-45 pubmed publisher
  16. Colot H, Stutz F, Rosbash M. The yeast splicing factor Mud13p is a commitment complex component and corresponds to CBP20, the small subunit of the nuclear cap-binding complex. Genes Dev. 1996;10:1699-708 pubmed
    ..Taken together with the accompanying results for a mammalian system, our data indicate that cap-binding proteins as well as the pre-mRNA cap contribute to early steps in spliceosome assembly. ..
  17. Kuhn J, Hugouvieux V, Schroeder J. mRNA cap binding proteins: effects on abscisic acid signal transduction, mRNA processing, and microarray analyses. Curr Top Microbiol Immunol. 2008;326:139-50 pubmed
    ..In conclusion, mutants in genes participating in RNA processing provide excellent tools to uncover novel molecular mechanisms for the regulation of RNA metabolism and of signal transduction networks in wild-type plants. ..
  18. Büssing I, Yang J, Lai E, Grosshans H. The nuclear export receptor XPO-1 supports primary miRNA processing in C. elegans and Drosophila. EMBO J. 2010;29:1830-9 pubmed publisher
    ..Our findings demonstrate that XPO-1/Emb promotes the pri-miRNA-to-pre-miRNA processing and we propose that this function involves intranuclear transport and/or nuclear export of primary miRNAs. ..
  19. Hall K. RNA-protein interactions. Curr Opin Struct Biol. 2002;12:283-8 pubmed
    ..Even the common RNA-binding domains (RBDs) and the double stranded RNA binding motifs (dsRBMs) have been shown to exhibit a plethora of binding modes. ..
  20. Hosoda N, Kim Y, Lejeune F, Maquat L. CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells. Nat Struct Mol Biol. 2005;12:893-901 pubmed
    ..SMD depends on the recruitment of Upf1 by the RNA-binding protein Stau1 but does not depend on the other Upf proteins. We find that CBP80 interacts with Upf1 and promotes the interaction of Upf1 with Upf2 but not with Stau1...
  21. Choe J, Cho H, Lee H, Kim Y. microRNA/Argonaute 2 regulates nonsense-mediated messenger RNA decay. EMBO Rep. 2010;11:380-6 pubmed publisher
    ..The regulation of NMD by miRNAs will shed light on a new post-transcriptional regulation mechanism of gene expression in mammalian cells. ..
  22. Hossain M, Claggett J, Nguyen T, Johnson T. The cap binding complex influences H2B ubiquitination by facilitating splicing of the SUS1 pre-mRNA. RNA. 2009;15:1515-27 pubmed publisher
  23. Oh N, Kim K, Cho H, Choe J, Kim Y. Pioneer round of translation occurs during serum starvation. Biochem Biophys Res Commun. 2007;362:145-51 pubmed
    ..These results suggest that mRNAs enter the pioneer round of translation during serum starvation and are targeted for NMD if they contain premature termination codons. ..
  24. Di Penta A, Mercaldo V, Florenzano F, Munck S, Ciotti M, Zalfa F, et al. Dendritic LSm1/CBP80-mRNPs mark the early steps of transport commitment and translational control. J Cell Biol. 2009;184:423-35 pubmed publisher
  25. Dias S, Wilson K, Rojas K, Ambrosio A, Cerione R. The molecular basis for the regulation of the cap-binding complex by the importins. Nat Struct Mol Biol. 2009;16:930-7 pubmed publisher
    ..Together, these studies enable us to propose a model describing how importin-beta stimulates the dissociation of capped RNA from the CBC in the cytosol following its nuclear export. ..
  26. Wu X, Jiang Y. Overproduction of non-translatable mRNA silences. The transcription of Ty1 retrotransposons in S. cerevisiae via functional inactivation of the nuclear cap-binding complex and subsequent hyperstimulation of the TORC1 pathway. Yeast. 2008;25:327-47 pubmed publisher
    ..Although overproduction of non-translatable mRNA causes transient Ty1 transcriptional silencing, it does not play a detectable role in controlling Ty1 retrotransposition. ..
  27. Imataka H. [Eukaryotic translation and nuclear events]. Tanpakushitsu Kakusan Koso. 2004;49:1296-301 pubmed
  28. Marin Vinader L, van Genesen S, Lubsen N. mRNA made during heat shock enters the first round of translation. Biochim Biophys Acta. 2006;1759:535-42 pubmed
    ..CBP20 is part of the cap binding complex which is thought to direct the first round of translation. Together our data suggest that all mRNAs made during heat shock enter the pioneer round of translation. ..
  29. Dzikiewicz Krawczyk A, Piontek P, Szweykowska Kulinska Z, Jarmołowski A. The nuclear cap-binding protein complex is not essential for nonsense-mediated mRNA decay (NMD) in plants. Acta Biochim Pol. 2008;55:825-8 pubmed
    ..Our results suggest that neither CBP20 nor CBP80 is involved in NMD in A. thaliana. ..
  30. Boyne J, Colgan K, Whitehouse A. Recruitment of the complete hTREX complex is required for Kaposi's sarcoma-associated herpesvirus intronless mRNA nuclear export and virus replication. PLoS Pathog. 2008;4:e1000194 pubmed publisher
    ..Together, these data provide the first direct evidence that the complete hTREX complex is essential for the export of KSHV intronless mRNAs and infectious virus production. ..
  31. Roth M, Carpentier P, Kaïkati O, Joly J, Charrault P, Pirocchi M, et al. FIP: a highly automated beamline for multiwavelength anomalous diffraction experiments. Acta Crystallogr D Biol Crystallogr. 2002;58:805-14 pubmed
    ..This is illustrated by the large number of challenging structures that have been solved since 1999. ..
  32. Strasser A, Dickmanns A, Luhrmann R, Ficner R. Structural basis for m3G-cap-mediated nuclear import of spliceosomal UsnRNPs by snurportin1. EMBO J. 2005;24:2235-43 pubmed
    ..The critical role of this tryptophan and as well of a tryptophan continuing the RNA base stack was confirmed by nuclear import assays and cap-binding activity tests using several snurportin1 mutants. ..
  33. Strasser A, Dickmanns A, Schmidt U, Penka E, Urlaub H, Sekine M, et al. Purification, crystallization and preliminary crystallographic data of the m3G cap-binding domain of human snRNP import factor snurportin 1. Acta Crystallogr D Biol Crystallogr. 2004;60:1628-31 pubmed
    ..47, c = 130.09 A, alpha = beta = gamma = 90 degrees. Crystals contain one molecule in the asymmetric unit and diffract to a resolution limit of 2.9 A. ..
  34. von der Haar T, McCarthy J. Intracellular translation initiation factor levels in Saccharomyces cerevisiae and their role in cap-complex function. Mol Microbiol. 2002;46:531-44 pubmed
    ..Overall, these data constitute an important basis for developing a quantitative model of the workings of the eukaryotic translation apparatus. ..
  35. Ghosh B, Benyumov A, Ghosh P, Jia Y, Avdulov S, Dahlberg P, et al. Nontoxic chemical interdiction of the epithelial-to-mesenchymal transition by targeting cap-dependent translation. ACS Chem Biol. 2009;4:367-77 pubmed publisher
    ..Our work provides strong motivation for the continued development of compounds designed to normalize cap-dependent translation as novel chemo-preventive agents and therapeutics for cancer and fibrosis. ..
  36. Maquat L. Nonsense-mediated mRNA decay. Curr Biol. 2002;12:R196-7 pubmed
  37. Sato H, Maquat L. Remodeling of the pioneer translation initiation complex involves translation and the karyopherin importin beta. Genes Dev. 2009;23:2537-50 pubmed publisher
    ..Our studies uncover a previously unappreciated role for IMPbeta and a novel paradigm for how newly synthesized messenger ribonucleoproteins (mRNPs) are matured. ..
  38. Ptushkina M, von der Haar T, Vasilescu S, Frank R, Birkenhäger R, McCarthy J. Cooperative modulation by eIF4G of eIF4E-binding to the mRNA 5' cap in yeast involves a site partially shared by p20. EMBO J. 1998;17:4798-808 pubmed
    ..The results presented provide a basis for understanding how cycling of eIF4E and eIF4G occurs in yeast translation and explains how p20 can act as a fine, but not as a coarse, regulator of protein synthesis. ..
  39. Lejeune F, Maquat L. Immunopurification and analysis of protein and RNA components of mRNP in mammalian cells. Methods Mol Biol. 2004;257:115-24 pubmed
    ..We also describe a modification using beta-mercaptoethanol that facilitates analyzing proteins that comigrate with antibody light or heavy chains. ..
  40. Kataoka N, Ohno M, Moda I, Shimura Y. Identification of the factors that interact with NCBP, an 80 kDa nuclear cap binding protein. Nucleic Acids Res. 1995;23:3638-41 pubmed
    ..We also show that NCBP requires NIP1 for binding to the cap structure. Possible roles of NIPs in cap-dependent nuclear processes are discussed. ..
  41. Ka M, Park Y, Kim J. The DEAD-box RNA helicase, Dhh1, functions in mating by regulating Ste12 translation in Saccharomyces cerevisiae. Biochem Biophys Res Commun. 2008;367:680-6 pubmed publisher
    ..We propose that Dhh1 and Caf20 regulate the Ste12 protein expression and the Ste12 protein level is associated with P-body formation during mating. ..
  42. Chen Y, Zeng S, Hsu J, Horng J, Yang H, Shih S, et al. Amantadine as a regulator of internal ribosome entry site. Acta Pharmacol Sin. 2008;29:1327-33 pubmed publisher
    ..25 mg/mL. These results imply that amantadine may distinguish between cap-dependent translation and cap-independent IRES-mediated translation and can be used to regulate gene expression at a translational level. ..
  43. Narita T, Yung T, Yamamoto J, Tsuboi Y, Tanabe H, Tanaka K, et al. NELF interacts with CBC and participates in 3' end processing of replication-dependent histone mRNAs. Mol Cell. 2007;26:349-65 pubmed
    ..Our results point to a surprising role of NELF in the 3' end processing of histone mRNAs and also suggest that NELF is a new factor that coordinates different mRNA processing steps during transcription. ..
  44. Park Y, Hur H, Ka M, Kim J. Identification of translational regulation target genes during filamentous growth in Saccharomyces cerevisiae: regulatory role of Caf20 and Dhh1. Eukaryot Cell. 2006;5:2120-7 pubmed
    ..The filamentation defects caused by caf20 and dhh1 mutations were suppressed by STE12 overexpression. These results suggest that Caf20 and Dhh1 control yeast filamentation by regulating STE12 translation. ..
  45. Ramirez C, Vilela C, Berthelot K, McCarthy J. Modulation of eukaryotic mRNA stability via the cap-binding translation complex eIF4F. J Mol Biol. 2002;318:951-62 pubmed
    ..Thus, the accessibility of the cap to Dcp1 in vivo is not simply controlled by competition with eIF4E, but is subject to switching between molecular states with different levels of access. ..
  46. Chen J, He Y, Simons S. Structure/activity relationships for GMEB-2: the second member of the glucocorticoid modulatory element-binding complex. Biochemistry. 2004;43:245-55 pubmed
    ..Finally, as the domain organization of GMEB-2 and -1 is extremely similar, we conclude that the quantitative differences in activities derive from variations in amino acid sequence rather than more global features of protein structure. ..
  47. Harris R, Esposito D, Sankar A, Maman J, Hinks J, Pearl L, et al. The 3D solution structure of the C-terminal region of Ku86 (Ku86CTR). J Mol Biol. 2004;335:573-82 pubmed
    ..Two prominent hydrophobic pockets in the gap between helices alpha2 and alpha4 suggest a potential ligand-binding characteristic for this globular domain. ..
  48. Montgomery T, Carrington J. Splicing and dicing with a SERRATEd edge. Proc Natl Acad Sci U S A. 2008;105:8489-90 pubmed publisher
  49. Woeller C, Gaspari M, Isken O, Maquat L. NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA. EMBO Rep. 2008;9:446-51 pubmed publisher
    ..We show that EMCV IRES-initiated translation undergoes a CBP80/20-associated pioneer round of translation that results in CBP80/20-dependent and Upf factor-dependent NMD when translation terminates prematurely...
  50. Lee H, Cho H, Kim Y. Ectopic expression of eIF4E-transporter triggers the movement of eIF4E into P-bodies, inhibiting steady-state translation but not the pioneer round of translation. Biochem Biophys Res Commun. 2008;369:1160-5 pubmed publisher
    ..These results suggest that the pioneer round of translation differs from steady-state translation in terms of ribosome recruitment. ..
  51. Oh N, Kim K, Choe J, Kim Y. Pioneer round of translation mediated by nuclear cap-binding proteins CBP80/20 occurs during prolonged hypoxia. FEBS Lett. 2007;581:5158-64 pubmed
    ..These results indicate that mRNAs enter the pioneer round of translation during prolonged hypoxia. ..
  52. McKee A, Kleckner N. Mutations in Saccharomyces cerevisiae that block meiotic prophase chromosome metabolism and confer cell cycle arrest at pachytene identify two new meiosis-specific genes SAE1 and SAE3. Genetics. 1997;146:817-34 pubmed
    ..SAE1 encodes a 208-residue protein homologous to vertebrate mRNA cap-binding protein 20. SAE3 corresponds to a meiosis-specific RNA encoding an unusually short open reading frame of 50 codons. ..
  53. Worch R, Stepinski J, Niedzwiecka A, Jankowska Anyszka M, Mazza C, Cusack S, et al. Novel way of capping mRNA trimer and studies of its interaction with human nuclear cap-binding complex. Nucleosides Nucleotides Nucleic Acids. 2005;24:1131-4 pubmed
    ..To examine a possible role of a longer mRNA chain in the CBC-cap recognition, we have synthesized an mRNA tetramer using a novel way of capping an RNA trimer and determined its affinity for CBC by fluorescence titration. ..
  54. Marintchev A, Wagner G. eIF4G and CBP80 share a common origin and similar domain organization: implications for the structure and function of eIF4G. Biochemistry. 2005;44:12265-72 pubmed
  55. Hwang J, Sato H, Tang Y, Matsuda D, Maquat L. UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps. Mol Cell. 2010;39:396-409 pubmed publisher
    ..A unifying model proposes a choreographed series of protein-protein interactions occurring on an NMD target...
  56. Baron Benhamou J, Fortes P, Inada T, Preiss T, Hentze M. The interaction of the cap-binding complex (CBC) with eIF4G is dispensable for translation in yeast. RNA. 2003;9:654-62 pubmed
  57. Görnemann J, Kotovic K, Hujer K, Neugebauer K. Cotranscriptional spliceosome assembly occurs in a stepwise fashion and requires the cap binding complex. Mol Cell. 2005;19:53-63 pubmed
    ..Thus, the demonstration of an essential link between CBC and spliceosome assembly in vivo indicates that 5' end capping couples pre-mRNA splicing to transcription. ..