Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

An extensive network of coupling among gene expression machines

Abstract

Gene expression in eukaryotes requires several multi-component cellular machines. Each machine carries out a separate step in the gene expression pathway, which includes transcription, several pre-messenger RNA processing steps and the export of mature mRNA to the cytoplasm. Recent studies lead to the view that, in contrast to a simple linear assembly line, a complex and extensively coupled network has evolved to coordinate the activities of the gene expression machines. The extensive coupling is consistent with a model in which the machines are tethered to each other to form ‘gene expression factories’ that maximize the efficiency and specificity of each step in gene expression.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A complex network of coupled interactions in gene expression.
Figure 2: Gene expression factory model for coupling steps in gene expression.
Figure 3: Model for coupling splicing to mRNA export and nonsense-mediated decay.

Similar content being viewed by others

References

  1. Bentley, D. Coupling RNA polymerase II transcription with pre-mRNA processing. Curr. Opin. Cell Biol. 11, 347–351 (1999).

    Article  CAS  PubMed  Google Scholar 

  2. Hirose, Y. & Manley, J. L. RNA polymerase II and the integration of nuclear events. Genes Dev. 14, 1415–1429 (2000).

    Article  CAS  PubMed  Google Scholar 

  3. Proudfoot, N. Connecting transcription to messenger RNA processing. Trends Biochem. Sci. 25, 290–293 (2000).

    Article  CAS  PubMed  Google Scholar 

  4. Shatkin, A. J. & Manley, J. L. The ends of the affair: capping and polyadenylation. Nature Struct. Biol. 7, 838–842 (2000).

    Article  CAS  PubMed  Google Scholar 

  5. Cramer, P. et al. Coordination between transcription and pre-mRNA processing. FEBS Lett. 498, 179–182 (2001).

    Article  CAS  PubMed  Google Scholar 

  6. Ptashne, M. & Gann, A. Genes and Signals (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2002).

    Google Scholar 

  7. Dahmus, M. E. Reversible phosphorylation of the C-terminal domain of RNA polymerase II. J. Biol. Chem. 271, 19009–19012 (1996).

    Article  CAS  PubMed  Google Scholar 

  8. Komarnitsky, P., Cho, E. J. & Buratowski, S. Different phosphorylated forms of RNA polymerase II and associated mRNA processing factors during transcription. Genes Dev. 14, 2452–2460 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cho, E. J., Kobor, M. S., Kim, M., Greenblatt, J. & Buratowski, S. Opposing effects of Ctk1 kinase and Fcp1 phosphatase at Ser 2 of the RNA polymerase II C-terminal domain. Genes Dev. 15, 3319–3329 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Trigon, S. et al. Characterization of the residues phosphorylated in vitro by different C-terminal domain kinases. J. Biol. Chem. 273, 6769–6775 (1998).

    Article  CAS  PubMed  Google Scholar 

  11. Price, D. H. P-TEFb, a cyclin-dependent kinase controlling elongation by RNA polymerase II. Mol. Cell. Biol. 20, 2629–2634 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. McCracken, S. et al. 5′-Capping enzymes are targeted to pre-mRNA by binding to the phosphorylated carboxy-terminal domain of RNA polymerase II. Genes Dev. 11, 3306–3318 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cho, E. J., Takagi, T., Moore, C. R. & Buratowski, S. mRNA capping enzyme is recruited to the transcription complex by phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev. 11, 3319–3326 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. McCracken, S. et al. The C-terminal domain of RNA polymerase II couples mRNA processing to transcription. Nature 385, 357–361 (1997).

    Article  ADS  CAS  PubMed  Google Scholar 

  15. Fong, N. & Bentley, D. L. Capping, splicing, and 3′ processing are independently stimulated by RNA polymerase II: different functions for different segments of the CTD. Genes Dev. 15, 1783–1795 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cramer, P., Bushnell, D. A. & Kornberg, R. D. Structural basis of transcription: RNA polymerase II at 2.8 angstrom resolution. Science 292, 1863–1876 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Ho, C. K. & Shuman, S. Distinct roles for CTD Ser-2 and Ser-5 phosphorylation in the recruitment and allosteric activation of mammalian mRNA capping enzyme. Mol. Cell 3, 405–411 (1999).

    Article  CAS  PubMed  Google Scholar 

  18. Schroeder, S. C., Schwer, B., Shuman, S. & Bentley, D. Dynamic association of capping enzymes with transcribing RNA polymerase II. Genes Dev. 14, 2435–2440 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cho, E. J., Rodriguez, C. R., Takagi, T. & Buratowski, S. Allosteric interactions between capping enzyme subunits and the RNA polymerase II carboxy-terminal domain. Genes Dev. 12, 3482–3487 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Taube, R., Lin, X., Irwin, D., Fujinaga, K. & Peterlin, B. M. Interaction between P-TEFb and the C-terminal domain of RNA polymerase II activates transcriptional elongation from sites upstream or downstream of target genes. Mol. Cell. Biol. 22, 321–331 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wada, T., Takagi, T., Yamaguchi, Y., Watanabe, D. & Handa, H. Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro. EMBO J. 17, 7395–7403 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kim, J. B. & Sharp, P. A. Positive transcription elongation factor B phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase. J. Biol. Chem. 276, 12317–12323 (2001).

    Article  CAS  PubMed  Google Scholar 

  23. Wen, Y. & Shatkin, A. J. Transcription elongation factor hSPT5 stimulates mRNA capping. Genes Dev. 13, 1774–1779 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Fong, Y. W. & Zhou, Q. Stimulatory effect of splicing factors on transcriptional elongation. Nature 414, 929–933 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  25. Barboric, M., Nissen, R. M., Kanazawa, S., Jabrane-Ferrat, N. & Peterlin, B. M. NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II. Mol. Cell 8, 327–337 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. Kim, J. B., Yamaguchi, Y., Wada, T., Handa, H. & Sharp, P. A. Tat-SF1 protein associates with RAP30 and human SPT5 proteins. Mol. Cell. Biol. 19, 5960–5968 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yan, D. et al. CUS2, a yeast homolog of human Tat-SF1, rescues function of misfolded U2 through an unusual RNA recognition motif. Mol. Cell. Biol. 18, 5000–5009 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ares, M. Jr, Grate, L. & Pauling, M. H. A handful of intron-containing genes produces the lion's share of yeast mRNA. RNA 5, 1138–1139 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Robert, F., Blanchette, M., Maes, O., Chabot, B. & Coulombe, B. A human RNA polymerase II-containing complex associated with factors necessary for spliceosome assembly. J. Biol. Chem. (in the press).

  30. Corden, J. L. & Patturajan, M. A CTD function linking transcription to splicing. Trends Biochem. Sci. 22, 413–416 (1997).

    Article  CAS  PubMed  Google Scholar 

  31. Morris, D. P. & Greenleaf, A. L. The splicing factor, Prp40, binds the phosphorylated carboxyl-terminal domain of RNA polymerase II. J. Biol. Chem. 275, 39935–39943 (2000).

    Article  CAS  PubMed  Google Scholar 

  32. Abovich, N. & Rosbash, M. Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals. Cell 89, 403–412 (1997).

    Article  CAS  PubMed  Google Scholar 

  33. Berget, S. M. Exon recognition in vertebrate splicing. J. Biol. Chem. 270, 2411–2414 (1995).

    Article  CAS  PubMed  Google Scholar 

  34. Goldstrohm, A. C., Greenleaf, A. L. & Garcia-Blanco, M. A. Co-transcriptional splicing of pre-messenger RNAs: considerations for the mechanism of alternative splicing. Gene 277, 31–47 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Lai, M. C., Teh, B. H. & Tarn, W. Y. A human papillomavirus E2 transcriptional activator. The interactions with cellular splicing factors and potential function in pre-mRNA processing. J. Biol. Chem. 274, 11832–11841 (1999).

    Article  CAS  PubMed  Google Scholar 

  36. Ge, H. Si, Y. & Wolffe, A. P. A novel transcriptional coactivator, p52, functionally interacts with the essential splicing factor ASF/SF2. Mol. Cell 2, 751–759 (1998).

    Article  CAS  PubMed  Google Scholar 

  37. Monsalve, M. et al. Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1. Mol. Cell 6, 307–316 (2000).

    Article  CAS  PubMed  Google Scholar 

  38. Martinez, E. et al. Human staga complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo. Mol. Cell. Biol. 21, 6782–6795 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Graveley, B. R. Sorting out the complexity of SR protein functions. RNA 6, 1197–1211 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Graveley, B. R., Hertel, K. J. & Maniatis, T. SR proteins are ‘locators’ of the RNA splicing machinery. Curr. Biol. 9, R6–R7 (1999).

    Article  CAS  PubMed  Google Scholar 

  41. Puigserver, P. et al. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92, 829–839 (1998).

    Article  CAS  PubMed  Google Scholar 

  42. Cramer, P., Pesce, C. G., Baralle, F. E. & Kornblihtt, A. R. Functional association between promoter structure and transcript alternative splicing. Proc. Natl Acad. Sci. USA 94, 11456–11460 (1997).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  43. Cramer, P. et al. Coupling of transcription with alternative splicing: RNA pol II promoters modulate SF2/ASF and 9G8 effects on an exonic splicing enhancer. Mol. Cell 4, 251–258 (1999).

    Article  CAS  PubMed  Google Scholar 

  44. Kadener, S. et al. Antagonistic effects of T-Ag and VP16 reveal a role for RNA pol II elongation on alternative splicing. EMBO J. 20, 5759–5768 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Eperon, L. P., Graham, I. R., Griffiths, A. D. & Eperon, I. C. Effects of RNA secondary structure on alternative splicing of pre-mRNA: is folding limited to a region behind the transcribing RNA polymerase? Cell 54, 393–401 (1988).

    Article  CAS  PubMed  Google Scholar 

  46. Roberts, G. C., Gooding, C., Mak, H. Y., Proudfoot, N. J. & Smith, C. W. Co-transcriptional commitment to alternative splice site selection. Nucleic Acids Res. 26, 5568–5572 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lewis, J. D., Izaurralde, E., Jarmolowski, A., McGuigan, C. & Mattaj, I. W. A nuclear cap-binding complex facilitates association of U1 snRNP with the cap-proximal 5′ splice site. Genes Dev. 10, 1683–1698 (1996).

    Article  CAS  PubMed  Google Scholar 

  48. Colot, H. V., 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. 10, 1699–1708 (1996).

    Article  CAS  PubMed  Google Scholar 

  49. Vagner, S., Vagner, C. & Mattaj, I. W. The carboxyl terminus of vertebrate poly(A) polymerase interacts with U2AF 65 to couple 3′-end processing and splicing. Genes Dev. 14, 403–413 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. McCracken, S., Lambermon, M. & Blencowe, B. J. SRm160 splicing coactivator promotes transcript 3′-end cleavage. Mol. Cell. Biol. 22, 148–160 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Reed, R. Mechanisms of fidelity in pre-mRNA splicing. Curr. Opin. Cell Biol. 12, 340–345 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Proudfoot, N. J. How RNA polymerase II terminates transcription in higher eukaryotes. Trends Biochem. Sci. 14, 105–110 (1989).

    Article  CAS  PubMed  Google Scholar 

  53. Birse, C. E., Minvielle-Sebastia, L., Lee, B. A., Keller, W. & Proudfoot, N. J. Coupling termination of transcription to messenger RNA maturation in yeast. Science 280, 298–301 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  54. McCracken, S. et al. Role of RNA polymerase II carboxy-terminal domain in coordinating transcription with RNA processing. Cold Spring Harbor Symp. Quant. Biol. 63, 301–309 (1998).

    Article  CAS  PubMed  Google Scholar 

  55. Dye, M. J. & Proudfoot, N. J. Multiple transcript cleavage precedes polymerase release in termination by RNA polymerase II. Cell 105, 669–681 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Osheim, Y. N., Proudfoot, N. J. & Beyer, A. L. EM visualization of transcription by RNA polymerase II: downstream termination requires a poly(A) signal but not transcript cleavage. Mol. Cell 3, 379–387 (1999).

    Article  CAS  PubMed  Google Scholar 

  57. Tran, D. P., Kim, S. J., Park, N. J., Jew, T. M. & Martinson, H. G. Mechanism of poly(A) signal transduction to RNA polymerase II in vitro. Mol. Cell. Biol. 21, 7495–7508 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Aranda, A. & Proudfoot, N. Transcriptional termination factors for RNA polymerase II in yeast. Mol. Cell 7, 1003–1011 (2001).

    Article  CAS  PubMed  Google Scholar 

  59. Calvo, O. & Manley, J. L. Evolutionarily conserved interaction between CstF-64 and PC4 links transcription, polyadenylation, and termination. Mol. Cell 7, 1013–1023 (2001).

    Article  CAS  PubMed  Google Scholar 

  60. Custodio, N. et al. Inefficient processing impairs release of RNA from the site of transcription. EMBO J. 18, 2855–2866 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Jensen, T. H., Patricio, K., McCarthy, T. & Rosbash, M. A block to mRNA nuclear export in S. cerevisiae leads to hyperadenylation of transcripts that accumulate at the site of transcription. Mol. Cell 7, 887–898 (2001).

    Article  CAS  PubMed  Google Scholar 

  62. Gall, J. G. A role for Cajal bodies in assembly of the nuclear transcription machinery. FEBS Lett. 498, 164–167 (2001).

    Article  CAS  PubMed  Google Scholar 

  63. Dundr, M. & Misteli, T. Functional architecture in the cell nucleus. Biochem. J. 356, 297–310 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Sleeman, J. E. & Lamond, A. I. Newly assembled snRNPs associate with coiled bodies before speckles, suggesting a nuclear snRNP maturation pathway. Curr. Biol. 9, 1065–1074 (1999).

    Article  CAS  PubMed  Google Scholar 

  65. Misteli, T., Caceres, J. F. & Spector, D. L. The dynamics of a pre-mRNA splicing factor in living cells. Nature 387, 523–527 (1997).

    Article  ADS  CAS  PubMed  Google Scholar 

  66. Misteli, T. et al. Serine phosphorylation of SR proteins is required for their recruitment to sites of transcription in vivo. J. Cell. Biol. 143, 297–307 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Misteli, T. & Spector, D. L. RNA polymerase II targets pre-mRNA splicing factors to transcription sites in vivo. Mol. Cell 3, 697–705 (1999).

    Article  CAS  PubMed  Google Scholar 

  68. Phair, R. D. & Misteli, T. High mobility of proteins in the mammalian cell nucleus. Nature 404, 604–609 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  69. Iborra, F. J., Pombo, A., Jackson, D. A. & Cook, P. R. Active RNA polymerases are localized within discrete transcription “factories” in human nuclei. J. Cell Sci. 109, 1427–1436 (1996).

    Article  CAS  PubMed  Google Scholar 

  70. Cook, P. R. The organization of replication and transcription. Science 284, 1790–1795 (1999).

    Article  CAS  PubMed  Google Scholar 

  71. Wetterberg, I., Zhao, J., Masich, S., Wieslander, L. & Skoglund, U. In situ transcription and splicing in the Balbiani ring 3 gene. EMBO J. 20, 2564–2574 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Luo, M. J. & Reed, R. Splicing is required for rapid and efficient mRNA export in metazoans. Proc. Natl Acad. Sci. USA 96, 14937–14942 (1999).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  73. Le Hir, H., Moore, M. J. & Maquat, L. E. Pre-mRNA splicing alters mRNP composition: evidence for stable association of proteins at exon–exon junctions. Genes Dev. 14, 1098–1108 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Zhou, Z. et al. The protein Aly links pre-messenger-RNA splicing to nuclear export in metazoans. Nature 407, 401–405 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  75. Le Hir, H., Izaurralde, E., Maquat, L. E. & Moore, M. J. The spliceosome deposits multiple proteins 20–24 nucleotides upstream of mRNA exon–exon junctions. EMBO J. 19, 6860–6869 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Luo, M. L. et al. Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature 413, 644–647 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  77. Strasser, K. & Hurt, E. Splicing factor Sub2p is required for nuclear mRNA export through its interaction with Yra1p. Nature 413, 648–652 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  78. Gatfield, D. et al. The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila. Curr. Biol. 11, 1716–1721 (2001).

    Article  CAS  PubMed  Google Scholar 

  79. Le Hir, H., Gatfield, D., Izaurralde, E. & Moore, M. J. The exon–exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay. EMBO J. 20, 4987–4997 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kataoka, N. et al. Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm. Mol. Cell 6, 673–682 (2000).

    Article  CAS  PubMed  Google Scholar 

  81. Lykke-Andersen, J., Shu, M. D. & Steitz, J. A. Communication of the position of exon–exon junctions to the mRNA surveillance machinery by the protein RNPS1. Science 293, 1836–1839 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  82. Kim, V. N. et al. The Y14 protein communicates to the cytoplasm the position of exon-exon junctions. EMBO J. 20, 2062–2068 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kim, V. N., Kataoka, N. & Dreyfuss, G. Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon–exon junction complex. Science 293, 1832–1836 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  84. Bachi, A. et al. The C-terminal domain of TAP interacts with the nuclear pore complex and promotes export of specific CTE-bearing RNA substrates. RNA 6, 136–158 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Segref, A. et al. Mex67p, a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores. EMBO J. 16, 3256–3271 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Jensen, T. H., Boulay, J., Rosbash, M. & Libri, D. The DECD box putative ATPase Sub2p is an early mRNA export factor. Curr. Biol. 11, 1711–1715 (2001).

    Article  CAS  PubMed  Google Scholar 

  87. Reed, R. & Magni, K. A new view of mRNA export: Separating the wheat from the chaff. Nature Cell Biol. 3, E201–E204 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Huang, Y. & Steitz, J. A. Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA. Mol. Cell 7, 899–905 (2001).

    Article  CAS  PubMed  Google Scholar 

  89. Hilleren, P., McCarthy, T., Rosbash, M., Parker, R. & Jensen, T. H. Quality control of mRNA 3′-end processing is linked to the nuclear exosome. Nature 413, 538–542 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  90. Lei, E. P., Krebber, H. & Silver, P. A. Messenger RNAs are recruited for nuclear export during transcription. Genes Dev. 15, 1771–1782 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Gross, S. & Moore, C. L. Rna15 interaction with the a-rich yeast polyadenylation signal is an essential step in mRNA 3′-end formation. Mol. Cell. Biol. 21, 8045–8055 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Kessler, M. M. et al. Hrp1, a sequence-specific RNA-binding protein that shuttles between the nucleus and the cytoplasm, is required for mRNA 3′-end formation in yeast. Genes Dev. 11, 2545–2556 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Gonzalez, C. I., Ruiz-Echevarria, M. J., Vasudevan, S., Henry, M. F. & Peiltz, S. W. The yeast hnRNP-like protein Hrp1/Nab4 marks a transcript for nonsense-mediated mRNA decay. Mol. Cell 5, 489–499 (2000).

    Article  CAS  PubMed  Google Scholar 

  94. Maquat, L. E. & Carmichael, G. G. Quality control of mRNA function. Cell 104, 173–176 (2001).

    Article  CAS  PubMed  Google Scholar 

  95. Serin, G., Gersappe, A., Black, J. D., Aronoff, R. & Maquat, L. E. Identification and characterization of human orthologues to Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4). Mol. Cell. Biol. 21, 209–223 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Lykke-Andersen, J., Shu, M. D. & Steitz, J. A. Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Cell 103, 1121–1131 (2000).

    Article  CAS  PubMed  Google Scholar 

  97. Hentze, M. W. & Kulozik, A. E. A perfect message: RNA surveillance and nonsense-mediated decay. Cell 96, 307–310 (1999).

    Article  CAS  PubMed  Google Scholar 

  98. Muhlemann, O. et al. Precursor RNAs harboring nonsense codons accumulate near the site of transcription. Mol. Cell 8, 33–43 (2001).

    Article  CAS  PubMed  Google Scholar 

  99. Ishigaki, Y., Li, X., Serin, G. & Maquat, L. E. Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20. Cell 106, 607–617 (2001).

    Article  CAS  PubMed  Google Scholar 

  100. Czaplinski, K., Ruiz-Echevarria, M. J., Gonzalez, C. I. & Peltz, S. W. Should we kill the messenger? The role of the surveillance complex in translation termination and mRNA turnover. Bioessays 21, 685–696 (1999).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank R. Axel, D. Bentley, S. Buratowski, B. Graveley, J. Manley, M. Ptashne and members of our labs for their comments on the manuscript. We also thank R. Hellmiss for the illustrations.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Tom Maniatis or Robin Reed.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maniatis, T., Reed, R. An extensive network of coupling among gene expression machines. Nature 416, 499–506 (2002). https://doi.org/10.1038/416499a

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/416499a

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing