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.

Garbled messages and corrupted translations

Nature Chemical Biology volume 6, pages 189–198 (2010)Cite this article

Subjects

An Erratum to this article was published on 01 April 2010

This article has been updated

Abstract

Following transcription, genomic information begins a long journey toward translation of its nucleotide sequence into the amino acids of a protein. In eukaryotes, synthesized pre-mRNAs become processed to mature mRNAs by 5′-end capping, splicing, 3′-end cleavage and polyadenylation in the nucleus, before being scrutinized for premature stop codons. Each step requires high precision and control to ensure that an intact and readable message is exported to the cytoplasm before finally becoming translated. Two important aspects of these processes are accurately managed by ribonucleoprotein machineries—the spliceosome and the ribosome. Recently, several natural products targeting these macromolecular assemblies have been reported. For the first time in eukaryotes, these molecules allow chemical disruption and dissection of the sophisticated machinery that regulates post-transcriptional events. Beyond their great potential as bioprobes for investigating mRNA regulation and protein synthesis, these compounds also show promise in opening new therapeutic approaches.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

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

Figure 1
Figure 2: Recognition of sequences around the intron-exon borders by splicing factors.
Figure 3: Simplified summary of eukaryotic translation initiation.
Figure 4: The eukaryotic translation elongation cycle.

Change history

  • 18 March 2010

    In the version of this article initially published, the page numbers in reference 69 were incorrect. The error has been corrected in the HTML and PDF versions of the article.

References

  1. Staley, J.P. & Woolford, J.L. Jr. Assembly of ribosomes and spliceosomes: complex ribonucleoprotein machines. Curr. Opin. Cell Biol. 21, 109–118 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Wahl, M.C., Will, C.L. & Lührmann, R. The spliceosome: design principles of a dynamic RNP machine. Cell 136, 701–718 (2009).

    CAS  PubMed  Google Scholar 

  3. Nakajima, H. et al. New antitumor substances, FR901463, FR901464 and FR901465. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities. J. Antibiot. (Tokyo) 49, 1196–1203 (1996).

    CAS  Google Scholar 

  4. Nakajima, H. et al. New antitumor substances, FR901463, FR901464 and FR901465. II. Activities against experimental tumors in mice and mechanism of action. J. Antibiot. (Tokyo) 49, 1204–1211 (1996).

    CAS  Google Scholar 

  5. Nakajima, H., Kim, Y.B., Terano, H., Yoshida, M. & Horinouchi, S. FR901228, a potent antitumor antibiotic, is a novel histone deacetylase inhibitor. Exp. Cell Res. 241, 126–133 (1998).

    CAS  PubMed  Google Scholar 

  6. Kaida, D. et al. Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nat. Chem. Biol. 3, 576–583 (2007).

    CAS  PubMed  Google Scholar 

  7. Horigome, M., Motoyoshi, H., Watanabe, H. & Kitahara, T. A synthesis of FR901464. Tetrahedr. Lett. 42, 8207–8210 (2001).

    CAS  Google Scholar 

  8. Thompson, C.F., Jamison, T.F. & Jacobsen, E.N. FR901464: total synthesis, proof of structure, and evaluation of synthetic analogues. J. Am. Chem. Soc. 123, 9974–9983 (2001).

    CAS  PubMed  Google Scholar 

  9. Albert, B.J., Sivaramakrishnan, A., Naka, T., Czaicki, N.L. & Koide, K. Total syntheses, fragmentation studies, and antitumor/antiproliferative activities of FR901464 and its low picomolar analogue. J. Am. Chem. Soc. 129, 2648–2659 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Albert, B.J. et al. Meayamycin inhibits pre-messenger RNA splicing and exhibits picomolar activity against multidrug-resistant cells. Mol. Cancer Ther. 8, 2308–2318 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Sakai, T. et al. Pladienolides, new substances from culture of Streptomyces platensis Mer-11107. I. Taxonomy, fermentation, isolation and screening. J. Antibiot. (Tokyo) 57, 173–179 (2004).

    CAS  Google Scholar 

  12. Sakai, T., Asai, N., Okuda, A., Kawamura, N. & Mizui, Y. Pladienolides, new substances from culture of Streptomyces platensis Mer-11107. II. Physico-chemical properties and structure elucidation. J. Antibiot. (Tokyo) 57, 180–187 (2004).

    CAS  Google Scholar 

  13. Kotake, Y. et al. Splicing factor SF3b as a target of the antitumor natural product pladienolide. Nat. Chem. Biol. 3, 570–575 (2007).

    CAS  PubMed  Google Scholar 

  14. O'Brien, K., Matlin, A.J., Lowell, A.M. & Moore, M.J. The biflavonoid isoginkgetin is a general inhibitor of Pre-mRNA splicing. J. Biol. Chem. 283, 33147–33154 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Soret, J. et al. Selective modification of alternative splicing by indole derivatives that target serine-arginine-rich protein splicing factors. Proc. Natl. Acad. Sci. USA 102, 8764–8769 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Stoilov, P., Lin, C.H., Damoiseaux, R., Nikolic, J. & Black, D.L. A high-throughput screening strategy identifies cardiotonic steroids as alternative splicing modulators. Proc. Natl. Acad. Sci. USA 105, 11218–11223 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Hagiwara, M. Alternative splicing: a new drug target of the post-genome era. Biochim. Biophys. Acta 1754, 324–331 (2005).

    CAS  PubMed  Google Scholar 

  18. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Choudhary, C. et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325, 834–840 (2009).

    CAS  PubMed  Google Scholar 

  20. Kuhn, A.N., van Santen, M.A., Schwienhorst, A., Urlaub, H. & Luhrmann, R. Stalling of spliceosome assembly at distinct stages by small-molecule inhibitors of protein acetylation and deacetylation. RNA 15, 153–175 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Balasubramanyam, K., Swaminathan, V., Ranganathan, A. & Kundu, T.K. Small molecule modulators of histone acetyltransferase p300. J. Biol. Chem. 278, 19134–19140 (2003).

    CAS  PubMed  Google Scholar 

  22. Balasubramanyam, K. et al. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J. Biol. Chem. 279, 33716–33726 (2004).

    CAS  PubMed  Google Scholar 

  23. Ban, N., Nissen, P., Hansen, J., Moore, P.B. & Steitz, T.A. The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. Science 289, 905–920 (2000).

    CAS  PubMed  Google Scholar 

  24. Brodersen, D.E. et al. The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit. Cell 103, 1143–1154 (2000).

    CAS  PubMed  Google Scholar 

  25. Wimberly, B.T. et al. Structure of the 30S ribosomal subunit. Nature 407, 327–339 (2000).

    CAS  PubMed  Google Scholar 

  26. Tu, D., Blaha, G., Moore, P.B. & Steitz, T.A. Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell 121, 257–270 (2005).

    CAS  PubMed  Google Scholar 

  27. Schroeder, S.J., Blaha, G., Tirado-Rives, J., Steitz, T.A. & Moore, P.B. The structures of antibiotics bound to the E site region of the 50 S ribosomal subunit of Haloarcula marismortui: 13-deoxytedanolide and girodazole. J. Mol. Biol. 367, 1471–1479 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Lecompte, O., Ripp, R., Thierry, J.C., Moras, D. & Poch, O. Comparative analysis of ribosomal proteins in complete genomes: an example of reductive evolution at the domain scale. Nucleic Acids Res. 30, 5382–5390 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Hermann, T. Drugs targeting the ribosome. Curr. Opin. Struct. Biol. 15, 355–366 (2005).

    CAS  PubMed  Google Scholar 

  30. Sutcliffe, J.A. Improving on nature: antibiotics that target the ribosome. Curr. Opin. Microbiol. 8, 534–542 (2005).

    CAS  PubMed  Google Scholar 

  31. Schroeder, R., Waldsich, C. & Wank, H. Modulation of RNA function by aminoglycoside antibiotics. EMBO J. 19, 1–9 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Chopra, I. & Roberts, M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol. Mol. Biol. Rev. 65, 232–260 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Nierhaus, D. & Nierhaus, K.H. Identification of the chloramphenicol-binding protein in Escherichia coli ribosomes by partial reconstitution. Proc. Natl. Acad. Sci. USA 70, 2224–2228 (1973).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Bashan, A. et al. Structural basis of the ribosomal machinery for peptide bond formation, translocation, and nascent chain progression. Mol. Cell 11, 91–102 (2003).

    CAS  PubMed  Google Scholar 

  35. Tenson, T., Lovmar, M. & Ehrenberg, M. The mechanism of action of macrolides, lincosamides and streptogramin B reveals the nascent peptide exit path in the ribosome. J. Mol. Biol. 330, 1005–1014 (2003).

    CAS  PubMed  Google Scholar 

  36. Hurdle, J.G., O' Neill, A.J. & Chopra, I. Prospects for aminoacyl-tRNA synthetase inhibitors as new antimicrobial agents. Antimicrob. Agents Chemother. 49, 4821–4833 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Rodnina, M.V. et al. Thiostrepton inhibits the turnover but not the GTPase of elongation factor G on the ribosome. Proc. Natl. Acad. Sci. USA 96, 9586–9590 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Heffron, S.E. & Jurnak, F. Structure of an EF-Tu complex with a thiazolyl peptide antibiotic determined at 2.35 A resolution: atomic basis for GE2270A inhibition of EF-Tu. Biochemistry 39, 37–45 (2000).

    CAS  PubMed  Google Scholar 

  39. Eustice, D.C. & Wilhelm, J.M. Mechanisms of action of aminoglycoside antibiotics in eucaryotic protein synthesis. Antimicrob. Agents Chemother. 26, 53–60 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Nathans, D. Puromycin inhibition of protein synthesis: incorporation of puromycin into peptide chains. Proc. Natl. Acad. Sci. USA 51, 585–592 (1964).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Justice, M.C. et al. Elongation factor 2 as a novel target for selective inhibition of fungal protein synthesis. J. Biol. Chem. 273, 3148–3151 (1998).

    CAS  PubMed  Google Scholar 

  42. Ahuja, D. et al. Inhibition of protein synthesis by didemnin B: how EF-1alpha mediates inhibition of translocation. Biochemistry 39, 4339–4346 (2000).

    CAS  PubMed  Google Scholar 

  43. Gomez-Lorenzo, M.G. et al. Three-dimensional cryo-electron microscopy localization of EF2 in the Saccharomyces cerevisiae 80S ribosome at 17.5 A resolution. EMBO J. 19, 2710–2718 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Jorgensen, R. et al. Two crystal structures demonstrate large conformational changes in the eukaryotic ribosomal translocase. Nat. Struct. Biol. 10, 379–385 (2003).

    CAS  PubMed  Google Scholar 

  45. Vazquez, D. Inhibitors of protein biosynthesis. Mol. Biol. Biochem. Biophys. 30, i–x, 1–312 (1979).

    Google Scholar 

  46. Takahashi, H. et al. Reveromycins, new inhibitors of eukaryotic cell growth. II. Biological activities. J. Antibiot. (Tokyo) 45, 1414–1419 (1992).

    CAS  Google Scholar 

  47. Miyamoto, Y. et al. Identification of Saccharomyces cerevisiae isoleucyl-tRNA synthetase as a target of the G1-specific inhibitor Reveromycin A. J. Biol. Chem. 277, 28810–28814 (2002).

    CAS  PubMed  Google Scholar 

  48. Hood, K.A., West, L.M., Northcote, P.T., Berridge, M.V. & Miller, J.H. Induction of apoptosis by the marine sponge (Mycale) metabolites, mycalamide A and pateamine. Apoptosis 6, 207–219 (2001).

    CAS  PubMed  Google Scholar 

  49. Sugawara, K. et al. Lactimidomycin, a new glutarimide group antibiotic. Production, isolation, structure and biological activity. J. Antibiot. (Tokyo) 45, 1433–1441 (1992).

    CAS  Google Scholar 

  50. Lee, K.H. et al. Inhibition of protein synthesis and activation of stress-activated protein kinases by onnamide A and theopederin B, antitumor marine natural products. Cancer Sci. 96, 357–364 (2005).

    CAS  PubMed  Google Scholar 

  51. Chan, J., Khan, S.N., Harvey, I., Merrick, W. & Pelletier, J. Eukaryotic protein synthesis inhibitors identified by comparison of cytotoxicity profiles. RNA 10, 528–543 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Kapp, L.D. & Lorsch, J.R. The molecular mechanics of eukaryotic translation. Annu. Rev. Biochem. 73, 657–704 (2004).

    CAS  PubMed  Google Scholar 

  53. Rogers, G.W. Jr., Richter, N.J., Lima, W.F. & Merrick, W.C. Modulation of the helicase activity of eIF4A by eIF4B, eIF4H, and eIF4F. J. Biol. Chem. 276, 30914–30922 (2001).

    CAS  PubMed  Google Scholar 

  54. Palacios, I.M., Gatfield, D., St Johnston, D. & Izaurralde, E. An eIF4AIII-containing complex required for mRNA localization and nonsense-mediated mRNA decay. Nature 427, 753–757 (2004).

    CAS  PubMed  Google Scholar 

  55. Northcote, P.T., Blunt, J.W. & Munro, M.H.G. Pateamine: a potent cytotoxin from the New Zealand marine sponge Mycale sp. Tetrahedr. Lett. 32, 6411–6414 (1991).

    CAS  Google Scholar 

  56. Rzasa, R.M., Shea, H.A. & Romo, D. Total synthesis of the novel, immunosuppressive agent (-)-pateamine A from Mycale sp. employing a β-lactam-based macrocyclization. J. Am. Chem. Soc. 120, 591–592 (1998).

    CAS  Google Scholar 

  57. Low, W.K. et al. Inhibition of eukaryotic translation initiation by the marine natural product pateamine A. Mol. Cell 20, 709–722 (2005).

    CAS  PubMed  Google Scholar 

  58. Bordeleau, M.E. et al. Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation. Proc. Natl. Acad. Sci. USA 102, 10460–10465 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Bordeleau, M.E. et al. RNA-mediated sequestration of the RNA helicase eIF4A by pateamine A inhibits translation initiation. Chem. Biol. 13, 1287–1295 (2006).

    CAS  PubMed  Google Scholar 

  60. Dang, Y. et al. Eukaryotic initiation factor 2α-independent pathway of stress granule induction by the natural product pateamine A. J. Biol. Chem. 281, 32870–32878 (2006).

    CAS  PubMed  Google Scholar 

  61. Mazroui, R. et al. Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2α phosphorylation. Mol. Biol. Cell 17, 4212–4219 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Kedersha, N. & Anderson, P. Stress granules: sites of mRNA triage that regulate mRNA stability and translatability. Biochem. Soc. Trans. 30, 963–969 (2002).

    CAS  PubMed  Google Scholar 

  63. Dang, Y. et al. Inhibition of nonsense-mediated mRNA decay by the natural product pateamine A through eukaryotic initiation factor 4AIII. J. Biol. Chem. 284, 23613–23621 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Kuznetsov, G. et al. Potent in vitro and in vivo anticancer activities of des-methyl, des-amino pateamine A, a synthetic analogue of marine natural product pateamine A. Mol. Cancer Ther. 8, 1250–1260 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Bordeleau, M.E. et al. Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4A. Nat. Chem. Biol. 2, 213–220 (2006).

    CAS  PubMed  Google Scholar 

  66. Lindqvist, L. et al. Selective pharmacological targeting of a DEAD box RNA helicase. PLoS One 3, e1583 (2008).

    PubMed  PubMed Central  Google Scholar 

  67. Obrig, T.G., Culp, W.J., McKeehan, W.L. & Hardesty, B. The mechanism by which cycloheximide and related glutarimide antibiotics inhibit peptide synthesis on reticulocyte ribosomes. J. Biol. Chem. 246, 174–181 (1971).

    CAS  PubMed  Google Scholar 

  68. Pestova, T.V. & Hellen, C.U. Translation elongation after assembly of ribosomes on the Cricket paralysis virus internal ribosomal entry site without initiation factors or initiator tRNA. Genes Dev. 17, 181–186 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Schneider-Poetsch, T. et al. Inhibition of translation elongation by cycloheximide and lactimidomycin. Nat. Chem. Biol. 6, 209–217 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Nakae, K. et al. Migrastatin, a new inhibitor of tumor cell migration from Streptomyces sp. MK929–43F1. Taxonomy, fermentation, isolation and biological activities. J. Antibiot. (Tokyo) 53, 1130–1136 (2000).

    CAS  Google Scholar 

  71. Woo, E.J. et al. Migrastatin and a new compound, isomigrastatin, from Streptomyces platensis. J. Antibiot. (Tokyo) 55, 141–146 (2002).

    CAS  Google Scholar 

  72. Takemoto, Y., Tashiro, E. & Imoto, M. Suppression of multidrug resistance by migrastatin. J. Antibiot. (Tokyo) 59, 435–438 (2006).

    CAS  Google Scholar 

  73. Shan, D. et al. Synthetic analogues of migrastatin that inhibit mammary tumor metastasis in mice. Proc. Natl. Acad. Sci. USA 102, 3772–3776 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Ju, J., Lim, S.K., Jiang, H. & Shen, B. Migrastatin and dorrigocins are shunt metabolites of iso-migrastatin. J. Am. Chem. Soc. 127, 1622–1623 (2005).

    CAS  PubMed  Google Scholar 

  75. Ju, J. et al. Lactimidomycin, iso-migrastatin and related glutarimide-containing 12-membered macrolides are extremely potent inhibitors of cell migration. J. Am. Chem. Soc. 131, 1370–1371 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Gurel, G., Blaha, G., Steitz, T.A. & Moore, P.B. The structures of triacetyloleandomycin and mycalamide A bound to the large ribosomal subunit of Haloarcula marismortui. Antimicrob. Agents Chemother. 53, 5010–5014 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Nishimura, S. et al. 13-Deoxytedanolide, a marine sponge-derived antitumor macrolide, binds to the 60S large ribosomal subunit. Bioorg. Med. Chem. 13, 449–454 (2005).

    CAS  PubMed  Google Scholar 

  78. Fresno, M., Jimenez, A. & Vazquez, D. Inhibition of translation in eukaryotic systems by harringtonine. Eur. J. Biochem. 72, 323–330 (1977).

    CAS  PubMed  Google Scholar 

  79. Gurel, G., Blaha, G., Moore, P.B. & Steitz, T.A. U2504 determines the species specificity of the A-site cleft antibiotics: the structures of tiamulin, homoharringtonine, and bruceantin bound to the ribosome. J. Mol. Biol. 389, 146–156 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Quintas-Cardama, A., Kantarjian, H. & Cortes, J. Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009. Cancer 115, 5382–5393 (2009).

    CAS  PubMed  Google Scholar 

  81. Kucuk, O. et al. Phase II trail of didemnin B in previously treated non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group (ECOG) study. Am. J. Clin. Oncol. 23, 273–277 (2000).

    CAS  PubMed  Google Scholar 

  82. Le Tourneau, C. et al. Reports of clinical benefit of plitidepsin (Aplidine), a new marine-derived anticancer agent, in patients with advanced medullary thyroid carcinoma. Am. J. Clin. Oncol. (2009).

  83. Ocio, E.M., Mateos, M.V., Maiso, P., Pandiella, A. & San-Miguel, J.F. New drugs in multiple myeloma: mechanisms of action and phase I/II clinical findings. Lancet Oncol. 9, 1157–1165 (2008).

    CAS  PubMed  Google Scholar 

  84. Robert, F. et al. Altering chemosensitivity by modulating translation elongation. PLoS One 4, e5428 (2009).

    PubMed  PubMed Central  Google Scholar 

  85. Beretta, L., Gingras, A.C., Svitkin, Y.V., Hall, M.N. & Sonenberg, N. Rapamycin blocks the phosphorylation of 4E–BP1 and inhibits cap-dependent initiation of translation. EMBO J. 15, 658–664 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Averous, J. & Proud, C.G. When translation meets transformation: the mTOR story. Oncogene 25, 6423–6435 (2006).

    CAS  PubMed  Google Scholar 

  87. Woo, J.T. et al. Reveromycin A, an agent for osteoporosis, inhibits bone resorption by inducing apoptosis specifically in osteoclasts. Proc. Natl. Acad. Sci. USA 103, 4729–4734 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Hiraoka, K. et al. Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages. Cancer Sci. 99, 1595–1602 (2008).

    CAS  PubMed  Google Scholar 

  89. Faustino, N.A. & Cooper, T.A. Pre-mRNA splicing and human disease. Genes Dev. 17, 419–437 (2003).

    CAS  PubMed  Google Scholar 

  90. Ng, B. et al. Increased noncanonical splicing of autoantigen transcripts provides the structural basis for expression of untolerized epitopes. J. Allergy Clin. Immunol. 114, 1463–1470 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Wang, G.S. & Cooper, T.A. Splicing in disease: disruption of the splicing code and the decoding machinery. Nat. Rev. Genet. 8, 749–761 (2007).

    CAS  PubMed  Google Scholar 

  92. Blencowe, B.J. Alternative splicing: new insights from global analyses. Cell 126, 37–47 (2006).

    CAS  PubMed  Google Scholar 

  93. Kim, Y.K. & Kim, V.N. Processing of intronic microRNAs. EMBO J. 26, 775–783 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Bayne, E.H. et al. Splicing factors facilitate RNAi-directed silencing in fission yeast. Science 322, 602–606 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Hirose, T., Shu, M.D. & Steitz, J.A. Splicing-dependent and -independent modes of assembly for intron-encoded box C/D snoRNPs in mammalian cells. Mol. Cell 12, 113–123 (2003).

    CAS  PubMed  Google Scholar 

  96. Kataoka, N., Fujita, M. & Ohno, M. Functional association of the Microprocessor complex with the spliceosome. Mol. Cell. Biol. 29, 3243–3254 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Lee, K.H. et al. Induction of a ribotoxic stress response that stimulates stress-activated protein kinases by 13-deoxytedanolide, an antitumor marine macrolide. Biosci. Biotechnol. Biochem. 70, 161–171 (2006).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank J.O. Liu of the Johns Hopkins University School of Medicine for his support and for making an unpublished manuscript available to us.

Author information

Authors and Affiliations

  1. Chemical Genetics Laboratory/Chemical Genomics Research Group, RIKEN Advanced Science Institute, Wako, Saitama, Japan

    Tilman Schneider-Poetsch & Minoru Yoshida

  2. Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Takeo Usui

  3. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

    Daisuke Kaida

  4. Centre for Renewable Energy Systems Technology (CREST) Research Project, Japan Science and Technology Corporation, Saitama, Japan

    Minoru Yoshida

Authors
  1. Tilman Schneider-Poetsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takeo Usui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daisuke Kaida
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Minoru Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Minoru Yoshida.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Schneider-Poetsch, T., Usui, T., Kaida, D. et al. Garbled messages and corrupted translations. Nat Chem Biol 6, 189–198 (2010). https://doi.org/10.1038/nchembio.326

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.326

This article is cited by

Search

Advanced 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