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  • Review Article
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RNA-quality control by the exosome

Nature Reviews Molecular Cell Biology volume 7, pages 529–539 (2006)Cite this article

Key Points

  • The processing and degradation of RNA sequences is ubiquitous, and these activities can be separated into different classes on the basis of their mechanism and function. The clearest functional differences exist between RNA maturation that will generate a usable RNA from its precursor and RNA degradation that will destroy the RNA completely.

  • There is mounting evidence that all RNA-maturation pathways in eukaryotes are continuously monitored by surveillance systems. A key component of the RNA-surveillance machinery is the exosome complex of 3′→5′ exonucleases. On different substrates this complex is responsible for either total RNA degradation or accurate RNA processing, implying a precise distinction between different classes of substrate.

  • Despite the presence of multiple catalytic sites, the purified yeast exosome is almost entirely inactive. However, several activating cofactors have recently been identified.

  • The role of polyadenylation in eukaryotic cells seems different on either side of the nuclear envelope. The long poly(A) tails on cytoplasmic mRNAs promote stability and translation. By contrast, defective nuclear RNAs are identified and 'tagged' with short oligo(A) tails by the TRAMP polyadenylation complex prior to degradation by the exosome. Such tagging of RNAs by polyadenylation could be conceptually similar to the role of polyubiquitylation in targeting proteins for degradation by the proteasome complex.

  • Key features of RNA degradation have been conserved throughout evolution. Recent structural analyses indicate that the eukaryotic exosome resembles a complex between bacterial PNPase and RNase II, the most active degradative exonucleases in Escherichia coli lysates. Moreover, the role of eukaryotic poly(A) polymerases in targeting nuclear RNAs for degradation is strikingly similar to the role of oligoadenylation in stimulating RNA degradation in bacteria.

Abstract

The exosome complex of 3′→5′ exonucleases is an important component of the RNA-processing machinery in eukaryotes. This complex functions in the accurate processing of nuclear RNA precursors and in the degradation of RNAs in both the nucleus and the cytoplasm. However, it has been unclear how different classes of substrate are distinguished from one another. Recent studies now provide insights into the regulation and structure of the exosome, and they reveal striking similarities between the process of RNA degradation in bacteria and eukaryotes.

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Figure 1: Structure of the exosome complex.
Figure 2: Activation of the exosome.
Figure 3: Roles of polyadenylation in eukaryotic cells.

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References

  1. Warner, J. R. The economics of ribosome biosynthesis in yeast. Trends Biochem. Sci. 24, 437?440 (1999).

    Article  CAS  PubMed  Google Scholar 

  2. Parker, R. & Song, H. The enzymes and control of eukaryotic mRNA turnover. Nature Struct. Mol. Biol. 11, 121?127 (2004).

    Article  CAS  Google Scholar 

  3. Mitchell, P., Petfalski, E., Shevchenko, A., Mann, M. & Tollervey, D. The exosome; a conserved eukaryotic RNA processing complex containing multiple 3′→5′ exoribonuclease activities. Cell 91, 457?466 (1997).

    Article  CAS  PubMed  Google Scholar 

  4. Allmang, C. et al. The yeast exosome and human PM-Scl are related complexes of 3′→5′ exonucleases. Genes Dev. 13, 2148?2158 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Peng, W. T. et al. A panoramic view of yeast noncoding RNA processing. Cell 113, 919?933 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Burkard, K. T. & Butler, J. S. A nuclear 3′?5′ exonuclease involved in mRNA degradation interacts with Poly(A) polymerase and the hnRNA protein Npl3p. Mol. Cell. Biol. 20, 604?616 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Araki, Y. et al. Ski7p G protein interacts with the exosome and the Ski complex for 3′-to-5′ mRNA decay in yeast. EMBO J. 20, 4684?4693 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. van Hoof, A., Staples, R. R., Baker, R. E. & Parker, R. Function of the ski4p (Csl4p) and Ski7p proteins in 3′-to-5′ degradation of mRNA. Mol. Cell. Biol. 20, 8230?8243 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mitchell, P. et al. Rrp47p is an exosome-associated protein required for the 3′ processing of stable RNAs. Mol. Cell. Biol. 23, 6982?6992 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yavuzer, U., Smith, G. C., Bliss, T., Werner, D. & Jackson, S. P. DNA end-independent activation of DNA-PK mediated via association with the DNA-binding protein C1D. Genes Dev. 12, 2188?2199 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. van Hoof, A., Lennertz, P. & Parker, R. Yeast exosome mutants accumulate 3′-extended polyadenylated forms of U4 small nuclear RNA and small nucleolar RNAs. Mol. Cell. Biol. 20, 441?452 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zanchin, N. I. & Goldfarb, D. S. The exosome subunit Rrp43p is required for the efficient maturation of 5.8S, 18S and 25S rRNA. Nucleic Acids Res. 27, 1283?1288 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Allmang, C. et al. Functions of the exosome in rRNA, snoRNA and snRNA synthesis. EMBO J. 18, 5399?5410 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. de la Cruz, J., Kressler, D., Tollervey, D. & Linder, P. Dob1p (Mtr4p) is a putative ATP-dependent RNA helicase required for the 3′ end formation of 5.8S rRNA in Saccharomyces cerevisiae. EMBO J. 17, 1128?1140 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Grosshans, H., Deinert, K., Hurt, E. & Simos, G. Biogenesis of the signal recognition particle (SRP) involves import of SRP proteins into the nucleolus, assembly with the SRP-RNA, and Xpo1p-mediated export. J. Cell Biol. 153, 745?762 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Allmang, C., Mitchell, P., Petfalski, E. & Tollervey, D. Degradation of ribosomal RNA precursors by the exosome. Nucleic Acids Res. 28, 1684?1691 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wyers, F. et al. Cryptic Pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 121, 725?737 (2005). Shows that the TRAMP complex and the exosome rapidly degrade transcripts that are produced from intergenic regions. These transcripts are very common, being produced from up to 10% of intergenic regions under normal conditions.

    Article  CAS  PubMed  Google Scholar 

  18. LaCava, J. et al. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 21, 713?724 (2005).

    Article  CAS  Google Scholar 

  19. Vanacova, S. et al. A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol. 3, e189 (2005). A biochemical analysis of the activity of the TRAMP complex, showing that it can recruit the exosome to degrade an aberrant tRNA in vitro.

    Article  PubMed  CAS  Google Scholar 

  20. Kadaba, S. et al. Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae. Genes Dev. 18, 1227?1240 (2004). First report that polyadenylation by Trf4 is linked to RNA degradation by the exosome.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Torchet, C. et al. Processing of 3′ extended read-through transcripts by the exosome can generate functional mRNAs. Mol. Cell 9, 1285?1296 (2002).

    Article  CAS  PubMed  Google Scholar 

  22. 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  CAS  PubMed  Google Scholar 

  23. Bousquet-Antonelli, C., Presutti, C. & Tollervey, D. Identification of a regulated pathway for nuclear pre-mRNA turnover. Cell 102, 765?775 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Lee, A., Henras, A. K. & Chanfreau, G. Multiple RNA surveillance pathways limit aberrant expression of iron uptake mRNAs and prevent iron toxicity in S. cerevisiae. Mol. Cell 19, 39?51 (2005). Reports that mRNA-encoding proteins that are involved in iron metabolism are subject to various different nuclear RNA-surveillance pathways.

    Article  CAS  PubMed  Google Scholar 

  25. Kuai, L., Das, B. & Sherman, F. A nuclear degradation pathway controls the abundance of normal mRNAs in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 102, 13962?13967 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Roth, K. M., Wolf, M. K., Rossi, M. & Butler, J. S. The nuclear exosome contributes to autogenous control of NAB2 mRNA levels. Mol. Cell. Biol. 25, 1577?1585 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Houalla, R. et al. Microarray detection of novel nuclear RNA substrates for the exosome. Yeast 23, 439?454 (2006).

    Article  CAS  PubMed  Google Scholar 

  28. Anderson, J. S. J. & Parker, R. P. The 3′ to 5′ degradation of yeast mRNAs is a general mechanism for mRNA turnover that requires the SKI2 DEVH box protein and 3′ to 5′ exonucleases of the exosome complex. EMBO J. 17, 1497?1506 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Takahashi, S., Araki, Y., Sakuno, T. & Katada, T. Interaction between Ski7p and Upf1p is required for nonsense-mediated 3′-to-5′ mRNA decay in yeast. EMBO J. 22, 3951?3959 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mitchell, P. & Tollervey, D. An NMD pathway in yeast involving accelerated deadenylation and exosome-mediated 3′→5′ degradation. Mol. Cell 11, 1405?1413 (2003).

    Article  CAS  PubMed  Google Scholar 

  31. Lejeune, F., Li, X. & Maquat, L. E. Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities. Mol. Cell 12, 675?687 (2003).

    Article  CAS  PubMed  Google Scholar 

  32. Frischmeyer, P. A. et al. An mRNA surveillance mechanism that eliminates transcripts lacking termination codons. Science 295, 2258?2261 (2002).

    Article  CAS  PubMed  Google Scholar 

  33. van Hoof, A., Frischmeyer, P. A., Dietz, H. C. & Parker, R. Exosome-mediated recognition and degradation of mRNAs lacking a termination codon. Science 295, 2262?2264 (2002).

    Article  CAS  PubMed  Google Scholar 

  34. Tran, H., Schilling, M., Wirbelauer, C., Hess, D. & Nagamine, Y. Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU. Mol. Cell 13, 101?111 (2004).

    Article  CAS  PubMed  Google Scholar 

  35. Chen, C. Y. et al. AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107, 451?464 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Mukherjee, D. et al. The mammalian exosome mediates the efficient degradation of mRNAs that contain AU-rich elements. EMBO J. 21, 165?174 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gherzi, R. et al. A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery. Mol. Cell 14, 571?583 (2004).

    Article  CAS  PubMed  Google Scholar 

  38. Doma, M. K. & Parker, R. Endonucleolytic cleavage of eukaryotic mRNAs with stalls in translation elongation. Nature 440, 561?564 (2006). First report of a yeast mRNA-surveillance pathway that is initiated by RNA cleavage.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tollervey, D. RNA lost in translation. Nature 440, 425?426 (2006).

    Article  CAS  PubMed  Google Scholar 

  40. Orban, T. I. & Izaurralde, E. Decay of mRNAs targeted by RISC requires XRN1, the Ski complex, and the exosome. RNA 11, 459?469 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Symmons, M. F., Jones, G. H. & Luisi, B. F. A duplicated fold is the structural basis for polynucleotide phosphorylase catalytic activity, processivity, and regulation. Struct. Fold. Des. 8, 1215?1226 (2000).

    Article  CAS  Google Scholar 

  42. Stickney, L. M., Hankins, J. S., Miao, X. & Mackie, G. A. Function of the conserved S1 and KH domains in polynucleotide phosphorylase. J. Bacteriol. 187, 7214?7121 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Valentine, R. C., Thang, M. N. & Grunberg-Manago, M. Electron microscopy of Escherichia coli polynucleotide phosphorylase molecules and polyribonucleotide formation. J. Mol. Biol. 39, 389?391 (1969).

    Article  CAS  PubMed  Google Scholar 

  44. Spickler, C. & Mackie, G. A. Action of RNase II and polynucleotide phosphorylase against RNAs containing stem-loops of defined structure. J. Bacteriol. 182, 2422?2427 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lorentzen, E. et al. The archaeal exosome core is a hexameric ring structure with three catalytic subunits. Nature Struct. Mol. Biol. 12, 575?581 (2005). The first structure of the archaeal exosome, which showed that only one of the archaeal RNase PH-like exosome subunits is an active ribonuclease, although both are required for activity.

    Article  CAS  Google Scholar 

  46. Lorentzen, E. & Conti, E. Structural basis of 3′ end RNA recognition and exoribonucleolytic cleavage by an exosome RNase PH core. Mol. Cell 20, 473?481 (2005). Following from the previous analysis, the authors show here how the exosome binds and degrades substrate RNAs.

    Article  CAS  PubMed  Google Scholar 

  47. Buttner, K., Wenig, K. & Hopfner, K. P. Structural framework for the mechanism of archaeal exosomes in RNA processing. Mol. Cell 20, 461?471 (2005). This work characterizes the structure of the complete archaeal exosome.

    Article  PubMed  CAS  Google Scholar 

  48. Symmons, M. F., Williams, M. G., Luisi, B. F., Jones, G. H. & Carpousis, A. J. Running rings around RNA: a superfamily of phosphate-dependent RNases. Trends Biochem. Sci. 27, 11?18 (2002).

    Article  CAS  PubMed  Google Scholar 

  49. Aloy, P. et al. A complex prediction: three-dimensional model of the yeast exosome. EMBO Rep. 3, 628?635 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. van Hoof, A. & Parker, R. The exosome: a proteasome for RNA? Cell 99, 347?350 (1999).

    Article  CAS  PubMed  Google Scholar 

  51. Andrulis, E. D. et al. The RNA processing exosome is linked to elongating RNA polymerase II in Drosophila. Nature 420, 837?841 (2002).

    Article  CAS  PubMed  Google Scholar 

  52. Brouwer, R., Pruijn, G. J. & van Venrooij, W. J. The human exosome: an autoantigenic complex of exoribonucleases in myositis and scleroderma. Arthritis Res. 3, 102?106 (2001).

    Article  CAS  PubMed  Google Scholar 

  53. Brouwer, R. et al. Three novel components of the human exosome. J. Biol. Chem. 276, 6177?6184 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Estevez, A. M., Kempf, T. & Clayton, C. The exosome of Trypanosoma brucei. EMBO J. 20, 3831?3839 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chekanova, J. A., Dutko, J. A., Mian, I. S. & Belostotsky, D. A. Arabidopsis thaliana exosome subunit AtRrp4p is a hydrolytic 3′→5′ exonuclease containing S1 and KH RNA-binding domains. Nucleic Acids Res. 30, 695?700 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Briggs, M. W., Burkard, K. T. & Butler, J. S. Rrp6p, the yeast homologue of the human PM-Scl 100-kDa autoantigen, is essential for efficient 5.8 S rRNA 3′ end formation. J. Biol. Chem. 273, 13255?13263 (1998).

    Article  CAS  PubMed  Google Scholar 

  57. Phillips, S. & Butler, J. S. Contribution of domain structure to the RNA 3′ end processing and degradation functions of the nuclear exosome subunit Rrp6p. RNA 9, 1098?1107 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Raijmakers, R., Egberts, W. V., van Venrooij, W. J. & Pruijn, G. J. Protein?protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring. J. Mol. Biol. 323, 653?663 (2002).

    Article  CAS  PubMed  Google Scholar 

  59. Estevez, A. M., Lehner, B., Sanderson, C. M., Ruppert, T. & Clayton, C. The roles of intersubunit interactions in exosome stability. J. Biol. Chem. 278, 34943?34951 (2003).

    Article  CAS  PubMed  Google Scholar 

  60. Lehner, B. & Sanderson, C. M. A protein interaction framework for human mRNA degradation. Genome Res. 14, 1315?1323 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Milligan, L., Torchet, C., Allmang, C., Shipman, T. & Tollervey, D. A nuclear surveillance pathway for mRNAs with defective polyadenylation. Mol. Cell. Biol. 25, 9996?10004 (2005). Describes how the exosome responds to mRNA molecules with defective poly(A) tails.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Wang, L., Lewis, M. S. & Johnson, A. W. Domain interactions within the Ski2?3?8 complex and between the Ski complex and Ski7p. RNA 11, 1291?1302 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Arigo, J. T., Carroll, K. L., Ames, J. M. & Corden, J. L. Regulation of yeast NRD1 expression by premature transcription termination. Mol. Cell 21, 641?651 (2006). Reports that autoregulation of Nrd1 expression involves the RNA-binding proteins Nrd1 and Nab3 as well as the exosome.

    Article  CAS  PubMed  Google Scholar 

  64. Vasiljeva, L. & Buratowski, S. Nrd1 Interacts with the nuclear exosome for 3′ processing of RNA polymerase II transcripts. Mol. Cell 21, 239?248 (2006). Reports a second exosome-stimulating complex. The Nrd1 protein binds to a specific target-RNA sequence and recruits the exosome to facilitate degradation.

    Article  CAS  PubMed  Google Scholar 

  65. Morlando, M. et al. Coupling between snoRNP assembly and 3′ processing controls box C/D snoRNA biosynthesis in yeast. EMBO J. 23, 2392?2401 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Steinmetz, E. J., Conrad, N. K., Brow, D. A. & Corden, J. L. RNA-binding protein Nrd1 directs poly(A)-independent 3′-end formation of RNA polymerase II transcripts. Nature 413, 327?331 (2001).

    Article  CAS  PubMed  Google Scholar 

  67. Puig, S., Askeland, E. & Thiele, D. J. Coordinated remodeling of cellular metabolism during iron deficiency through targeted mRNA degradation. Cell 120, 99?110 (2005). Reports that an ARE-mediated mRNA-degradation system functions in yeast and involves the yeast homologue of the well characterized human ARE-binding protein TTP.

    Article  CAS  PubMed  Google Scholar 

  68. Houseley, J. & Tollervey, D. Yeast Trf5p is a nuclear poly(A) polymerase. EMBO Rep. 7, 205?211 (2005).

    Article  PubMed Central  CAS  Google Scholar 

  69. Egecioglu, D. E., Henras, A. K. & Chanfreau, G. F. Contributions of Trf4p- and Trf5p-dependent polyadenylation to the processing and degradative functions of the yeast nuclear exosome. RNA 12, 26?32 (2006). References 68 and 69 describe a second TRAMP complex, and show that the two TRAMP complexes have different substrate affinities.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Kadaba, S., Wang, X. & Anderson, J. T. Nuclear RNA surveillance in Saccharomyces cerevisiae: Trf4p-dependent polyadenylation of nascent hypomethylated tRNA and an aberrant form of 5S rRNA. RNA 12, 508?521 (2006). Extends the range of TRAMP substrates and shows that the complex acts on newly transcribed pre-tRNA.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Gavin, A. C. et al. Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415, 141?147 (2002).

    Article  CAS  PubMed  Google Scholar 

  72. Gavin, A. C. et al. Proteome survey reveals modularity of the yeast cell machinery. Nature 440, 631?636 (2006).

    Article  CAS  PubMed  Google Scholar 

  73. Schilders, G., Raijmakers, R., Raats, J. M. & Pruijn, G. J. MPP6 is an exosome-associated RNA-binding protein involved in 5.8S rRNA maturation. Nucleic Acids Res. 33, 6795?6804 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Thomson, E. & Tollervey, D. Nop53p is required for late 60S ribosome subunit maturation and nuclear export in yeast. RNA 11, 1215?1224 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Granato, D. C. et al. Nop53p, an essential nucleolar protein that interacts with Nop17p and Nip7p, is required for pre-rRNA processing in Saccharomyces cerevisiae. FEBS J. 272, 4450?4463 (2005).

    Article  CAS  PubMed  Google Scholar 

  76. Brown, J. T., Bai, X. & Johnson, A. W. The yeast antiviral proteins Ski2p, Ski3p, and Ski8p exist as a complex in vivo. RNA 6, 449?457 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Inada, T. & Aiba, H. Translation of aberrant mRNAs lacking a termination codon or with a shortened 3′-UTR is repressed after initiation in yeast. EMBO J. 24, 1584?1595 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Cao, D. & Parker, R. Computational modeling and experimental analysis of nonsense-mediated decay in yeast. Cell 113, 533?45 (2003).

    Article  CAS  PubMed  Google Scholar 

  79. Wickner, R. B. Double-stranded and single-stranded RNA viruses of Saccharomyces cerevisiae. Annu. Rev. Microbiol. 46, 347?375 (1992).

    Article  CAS  PubMed  Google Scholar 

  80. Benard, L., Carroll, K., Valle, R. C., Masison, D. C. & Wickner, R. B. The ski7 antiviral protein is an EF1-α homolog that blocks expression of non-Poly(A) mRNA in Saccharomyces cerevisiae. J. Virol. 73, 2893?2900 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ridley, S. P., Sommer, S. S. & Wickner, R. B. Superkiller mutations in Saccharomyces cerevisiae suppress exclusion of M2 double-stranded RNA by L-A-HN and confer cold sensitivity in the presence of M and L-A-HN. Mol. Cell. Biol. 4, 761?770 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Folichon, M. et al. Fate of mRNA extremities generated by intrinsic termination: detailed analysis of reactions catalyzed by ribonuclease II and poly(A) polymerase. Biochimie 87, 819?826 (2005).

    Article  CAS  PubMed  Google Scholar 

  83. Khemici, V. & Carpousis, A. J. The RNA degradosome and poly(A) polymerase of Escherichia coli are required in vivo for the degradation of small mRNA decay intermediates containing REP-stabilizers. Mol. Microbiol. 51, 777?790 (2004).

    Article  CAS  PubMed  Google Scholar 

  84. Kuai, L., Fang, F., Butler, J. S. & Sherman, F. Polyadenylation of rRNA in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 101, 8581?8586 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Haracska, L., Johnson, R. E., Prakash, L. & Prakash, S. Trf4 and Trf5 proteins of Saccharomyces cerevisiae exhibit poly(A) RNA polymerase activity but no DNA polymerase activity. Mol. Cell. Biol. 25, 10183?10189 (2005). Reports that both Trf4 and Trf5 are poly(A) polymerases.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. West, S., Gromak, N., Norbury, C. J. & Proudfoot, N. J. Adenylation and exosome-mediated degradation of co-transcriptionally cleaved pre-messenger RNA in human cells Mol. Cell 21, 437?443 (2006). Evidence is presented that human mRNA molecules that fail to be correctly cleaved and polyadenylated are rapidly targeted by the exosome for degradation.

    Article  CAS  PubMed  Google Scholar 

  87. Teixeira, A. et al. Autocatalytic RNA cleavage in the human β-globin pre-mRNA promotes transcription termination. Nature 432, 526?530 (2004).

    Article  CAS  PubMed  Google Scholar 

  88. West, S., Gromak, N. & Proudfoot, N. J. Human 5′→3′ exonuclease Xrn2 promotes transcription termination at co-transcriptional cleavage sites. Nature 432, 522?525 (2004). Resolving a long-standing argument, West et al . show that cleavage occurs prior to transcriptional termination, the continuing RNA polymerase is then chased down by a 5′→3′ exonuclease that triggers its release.

    Article  CAS  PubMed  Google Scholar 

  89. Portnoy, V. et al. RNA polyadenylation in Archaea: not observed in Haloferax while the exosome polynucleotidylates RNA in Sulfolobus. EMBO Rep. 6, 1188?1193 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Yehudai-Resheff, S., Hirsh, M. & Schuster, G. Polynucleotide phosphorylase functions as both an exonuclease and a poly(A) polymerase in spinach chloroplasts. Mol. Cell. Biol. 21, 5408?5416 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Mohanty, B. K. & Kushner, S. R. Polynucleotide phosphorylase functions both as a 3′→5′ exonuclease and a poly(A) polymerase in Escherichia coli. Proc. Natl Acad. Sci. USA 97, 11966?11971 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Bollenbach, T. J., Schuster, G. & Stern, D. B. Cooperation of endo- and exoribonucleases in chloroplast mRNA turnover. Prog. Nucleic Acid. Res. Mol. Biol. 78, 305?337 (2004).

    Article  CAS  PubMed  Google Scholar 

  93. Zhu, B. et al. The human PAF complex coordinates transcription with events downstream of RNA synthesis. Genes Dev. 19, 1668?1673 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Graham, A. C., Kiss, D. L. & Andrulis, E. D. Differential distribution of exosome subunits at the nuclear lamina and in cytoplasmic foci. Mol. Biol. Cell 17, 1399?1409 (2006). Reports that some exosome components show differential enrichments at distinct locations, which indicates that all human exosome components might not obligatorily function as a complex.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Rouhana, L. et al. Vertebrate GLD2 poly(A) polymerases in the germline and the brain. RNA 11, 1117?1130 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Kwak, J. E., Wang, L., Ballantyne, S., Kimble, J. & Wickens, M. Mammalian GLD-2 homologs are poly(A) polymerases. Proc. Natl Acad. Sci. USA 101, 4407?4412 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Dez, C., Houseley, J. & Tollervey, D. Surveillance of nuclear-restricted pre-ribosomes within a subnucleolar region of Saccharomyces cerevisiae. EMBO J. 25, 1534?1546 (2006). The authors show that defective pre-ribosomes are rapidly and completely degraded by the TRAMP and exosome in nucleolar 'No-bodies'.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Kadowaki, T. et al. Isolation and characterization of Saccharomyces cerevisiae mRNA transport-defective (mtr) mutants. J. Cell Biol. 126, 649?659 (1994).

    Article  CAS  PubMed  Google Scholar 

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    Jonathan Houseley, John LaCava & David Tollervey

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Glossary

Small nucleolar RNA

(snoRNA). A small RNA molecule that functions in ribosome biogenesis in the nucleolus. Most snoRNAs direct site-specific base modification in the pre-ribosomal RNAs, whereas a small number are required for pre-ribosomal RNA cleavage.

Small nuclear RNAs

Five small RNA species (U1, U2, U4, U5 and U6) that form the core of the pre-mRNA-splicing system in the nucleus.

Ribonucleoprotein particle

A complex of proteins and RNA. In many cases, the proteins can recognize their cognate mRNA molecules (selective binding) and mediate their delivery to specific regions within the cell.

Nonsense-mediated decay

The process by which the cell destroys mRNAs in which translation has been prematurely terminated owing to the presence of a nonsense codon within the coding region.

Non-stop decay

An RNA-degradation pathway for mRNAs that do not contain a translation-termination codon and in which the translating ribosomes stall at the end of the transcript.

No-go decay

An RNA-degradation pathway that is induced by the stalling of a translating ribosome. The RNA is cleaved in the vicinity of the stalled ribosome, and this is followed by exonuclease degradation of the cleaved fragments. The 5′ fragment is degraded by the exosome, whereas the 3′ fragment is degraded by the 5′ exonuclease Xrn1.

S1 domain

A putative RNA-binding domain that was initially identified in ribosomal protein S1, and that is present in a large number of RNA-associated proteins.

KH domain

An evolutionarily conserved single-stranded-RNA-binding domain that was originally identified in the human heterogeneous nuclear (hn)RNP K protein.

Proteasome

A large multisubunit protease complex that selectively degrades multi-ubiquitylated proteins. It contains a 20S particle that has catalytic activity and two regulatory 19S particles.

DExH-box RNA helicases

RNA helicases that are related to DEAD-box proteins, and that contain an Asp-Glu-x-His (DExH) conserved motif.

ARE-mediated mRNA degradation

A process of rapid degradation of mRNAs that is mediated by the recruitment of the exosome by factors that bind to A+U-rich sequence elements (AREs) that are generally located in the 3′ untranslated region of the mRNAs.

Zinc-knuckle domain

This CX2CX4HX4C motif binds two zinc atoms and has been implicated in interactions between proteins and with single-stranded nucleic acids.

5′ cap structure

A structure that is located at the 5′ end of eukaryotic mRNAs and that consists of m7GpppN (where m7G represents 7-methylguanosine, p represents a phosphate group and N represents any base).

P-body

(Processing body). The cytoplasmic site of mRNA degradation. mRNAs on which translation has ceased are released from the polysome pool and recruited to P-bodies, where they accumulate together with the mRNA decapping and 5′-degradation machinery.

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Houseley, J., LaCava, J. & Tollervey, D. RNA-quality control by the exosome. Nat Rev Mol Cell Biol 7, 529–539 (2006). https://doi.org/10.1038/nrm1964

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