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RNA Exosome pp 79–90Cite as

Functions of the Cytoplasmic Exosome

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 702))

Abstract

The exosome consists of a core of ten essential proteins that includes the ribonuclease Rrp44p and is present in both the cytoplasm and nucleus of eukaryotic cells. The cytoplasmic exosome has been extensively characterized in the budding yeast Saccharomyces cerevisiae and some characterization of its metazoan counterpart indicates that most functional aspects are conserved. These studies have implicated the cytoplasmic exosome in the turnover of normal cellular mRNAs, as well as several mRNA surveillance pathways. For this, the exosome needs a set of four proteins that do not partake in nuclear exosome functions. These cofactors presumably direct the exosome to specific cytoplasmic RNA substrates. Here, we review cofactors and functions of the cytoplasmic exosome and provide unanswered questions on the mechanisms of cytoplasmic exosome function.

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References

  1. Toh EA, Guerry P, Wickner RB. Chromosomal superkiller mutants of Saccharomyces cerevisiae. J Bacteriol 1978; 136(3): 1002–1007.

    Google Scholar 

  2. Toh EA, Wickner RB. “Superkiller” mutations suppress chromosomal mutations affecting double-stranded RNAkiller plasmid replication in saccharomyces cerevisiae. ProcNatlAcad Sci USA 1980; 77(1):527–530.

    Article  Google Scholar 

  3. Jacobs Anderson JS, Parker R. 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 1998; 17(5): 1497–1506.

    Article  Google Scholar 

  4. van Hoof A, Staples RR, Baker RE et al. Function of the ski4p (Csl4p) and Ski7p proteins in 3′-to-5′ degradation of mRNA. Mol Cell Biol 2000; 20(21):8230–8243.

    Article  PubMed  Google Scholar 

  5. Wilson MA, Meaux S, van Hoof A. A genomic screen in yeast reveals novel aspects of nonstop mRNA metabolism. Genetics 2007; 177(2):773–784.

    Article  PubMed  CAS  Google Scholar 

  6. Doma MK, Parker R. Endonucleolytic cleavage of eukaryotic mRNAs with stalls in translation elongation. Nature 2006; 440(7083):561–564.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. van Hoof A, Frischmeyer PA, Dietz HC et al. Exosome-mediated recognition and degradation of mRNAs lacking atermination codon. Science 2002; 295(5563):2262–2264.

    Article  PubMed  Google Scholar 

  9. Synowsky SA, Heck AJ. The yeast Ski complex is a hetero-tetramer. Protein Sci 2008; 17(1): 119–125.

    Article  PubMed  CAS  Google Scholar 

  10. Brown JT, Bai X, Johnson AW. The yeast antiviral proteins Ski2p, Ski3p and Ski8p exist as a complex in vivo. RNA 2000; 6(3):449–457.

    Article  PubMed  CAS  Google Scholar 

  11. Wang L, Lewis MS, Johnson AW. Domain interactions within the Ski2/3/8 complex and between the Ski complex and Ski7p. RNA 2005; 11(8): 1291–1302.

    Article  PubMed  CAS  Google Scholar 

  12. Jackson RN, Klauer AA, Hintze BJ et al. The crystal structure of Mtr4 reveals a novel arch domain required for rRNA processing. EMBO J 2010; in press.

    Google Scholar 

  13. Gatfield D, Izaurralde E. Nonsense-mediated messenger RNA decay is initiated by endonucleolytic cleavage in Drosophila. Nature 2004; 429(6991):575–578.

    Article  PubMed  CAS  Google Scholar 

  14. Orban TI, Izaurralde E. Decay of mRNAs targeted by RISC requires XRN1, the Ski complex and the exosome. RNA 2005; 11(4):459–469.

    Article  PubMed  CAS  Google Scholar 

  15. Seago JE, Chernukhin IV, Newbury SF. The Drosophila gene twister, an orthologue of the yeast helicase SKI2, is differentially expressed during development. Mech Dev 2001; 106(1–2):137–141.

    Article  PubMed  CAS  Google Scholar 

  16. Cristodero M, Clayton CE. Trypanosome MTR4 is involved in rRNA processing. Nucleic Acids Res 2007; 35(20):7023–7030.

    Article  PubMed  CAS  Google Scholar 

  17. Etheridge RD, Clemens DM, Gershon PD et al. Identification and characterization of nuclear noncanonical poly(A) polymerases from Trypanosoma brucei. Mol Biochem Parasitai 2009; 164(1):66–73.

    Article  CAS  Google Scholar 

  18. Haile S, Cristodero M, Clayton C et al. The subcellular localisation of trypanosome RRP6 and its association with the exosome. Mol Biochem Parasitol 2007; 151(1):52–58.

    Article  PubMed  CAS  Google Scholar 

  19. Araki Y, Takahashi S, Kobayashi T et al. Ski7p G protein interacts with the exosome and the Ski complex for 3′-to-5′ mRNA decay in yeast. EMBO J 2001; 20(17):4684–4693.

    Article  PubMed  CAS  Google Scholar 

  20. Benard L, Carroll K, Valle RC et al. The ski7 antiviral protein is an EF1-alpha homolog that blocks expression of nonPoly(A) mRNA in Saccharomyces cerevisiae. J Virol 1999; 73(4):2893–2900.

    PubMed  CAS  Google Scholar 

  21. Kellis M, Birren BW, Lander ES. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae. Nature 2004; 428(6983):617–624.

    Article  PubMed  CAS  Google Scholar 

  22. Wolfe KH, Shields DC. Molecular evidence for an ancient duplication of the entire yeast genome. Nature 1997;387(6634):708–713.

    Article  PubMed  CAS  Google Scholar 

  23. van Hoof A. Conserved functions of yeast genes support the duplication, degeneration and complementation model for gene duplication. Genetics 2005; 171(4): 1455–1461.

    Article  PubMed  Google Scholar 

  24. Cheng Z, Liu Y, Wang C et al. Crystal structure of Ski8p, a WD-repeat protein with dual roles in mRNA metabolism and meiotic recombination. Protein Sci 2004; 13(10):2673–2684.

    Article  PubMed  CAS  Google Scholar 

  25. Dunckley T, Parker R. The DCP2 protein is required for mRNA decapping in Saccharomyces cerevisiae and contains a functional MutT motif. EMBO J 1999; 18(19):5411–5422.

    Article  PubMed  CAS  Google Scholar 

  26. van Dijk E, Cougot N, Meyer S et al. Human Dcp2: a catalytically active mRNA decapping enzyme located in specific cytoplasmic structures. EMBO J 2002; 21(24):6915–6924.

    Article  PubMed  Google Scholar 

  27. Steiger M, Carr-Schmid A, Schwartz DC et al. Analysis of recombinant yeast decapping enzyme. RNA 2003; 9(2):231–237.

    Article  PubMed  CAS  Google Scholar 

  28. Decker CJ, Parker R. A turnover pathway for both stable and unstable mRNAs in yeast: evidence for a requirement for deadenylation. Genes Dev 1993; 7(8): 1632–1643.

    Article  PubMed  CAS  Google Scholar 

  29. Hsu CL, Stevens A. Yeast cells lacking 5′→3′ exoribonuclease 1 contain mRNA species that are poly(A) deficient and partially lack the 5′ cap structure. Mol Cell Biol 1993; 13(8):4826–4835.

    PubMed  CAS  Google Scholar 

  30. Muhlrad D, Decker CJ, Parker R. Deadenylation of the unstable mRNA encoded by the yeast MFA2 gene leads to decapping followed by 5′→3′ digestion of the transcript. Genes Dev 1994; 8(7):855–866.

    Article  PubMed  CAS  Google Scholar 

  31. Wang Z, Kiledjian M. Functional link between the mammalian exosome and mRNA decapping. Cell 2001; 107(6):751–762.

    Article  PubMed  CAS  Google Scholar 

  32. Liu H, Rodgers ND, Jiao X et al. The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of pyrophosphatases. EMBO J 2002; 21(17):4699–4708.

    Article  PubMed  CAS  Google Scholar 

  33. Johnson AW, Kolodner RD. Synthetic lethality of sep1 (xrn1) ski2 and sep1 (xrn1) ski3 mutants of Saccharomyces cerevisiae is independent of killer virus and suggests a general role for these genes in translation control. Mol Cell Biol 1995; 15(5):2719–2727.

    PubMed  CAS  Google Scholar 

  34. Cao D, Parker R. Computational modeling of eukaryotic mRNA turnover. RNA 2001; 7(9): 1192–1212.

    Article  PubMed  CAS  Google Scholar 

  35. Lebreton A, Tomecki R, Dziembowski A et al. Endonucleolytic RNA cleavage by a eukaryotic exosome. Nature 2008; 456(7224):993–996.

    Article  PubMed  CAS  Google Scholar 

  36. Schaeffer D, Tsanova B, Barbas A et al. The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities. Nat Struct Mol Biol 2009; 16(1):56–62.

    Article  PubMed  CAS  Google Scholar 

  37. Schneider C, Leung E, Brown J et al. The N-terminal PIN domain of the exosome subunit Rrp44 harbors endonuclease activity and tethers Rrp44 to the yeast core exosome. Nucleic Acids Res 2009; 37(4): 1127–1140.

    Article  PubMed  CAS  Google Scholar 

  38. Dziembowski A, Lorentzen E, Conti E et al. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nat Struct Mol Biol 2007; 14(1): 15–22.

    Article  PubMed  CAS  Google Scholar 

  39. Chen CY, Shyu AB. AU-rich elements: characterization and importance in mRNA degradation. Trends in biochemical sciences 1995; 20(11):465–470.

    Article  PubMed  CAS  Google Scholar 

  40. Shaw G, Kamen R. A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 1986; 46(5):659–667.

    Article  PubMed  CAS  Google Scholar 

  41. Chen CY, Gherzi R, Ong SE et al. AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 2001; 107(4):451–464.

    Article  PubMed  CAS  Google Scholar 

  42. Gherzi R, Lee KY, Briata P et al. A KH Domain RNA Binding Protein, KSRP, Promotes ARE-Directed mRNA Turnover by Recruiting the Degradation Machinery. Mol Cell 2004; 14(5):571–583.

    Article  PubMed  CAS  Google Scholar 

  43. Mukherjee D, Gao M, O’Connor JP et al. The mammalian exosome mediates the efficient degradation of mRNAs that contain AU-rich elements. EMBO J 2002; 21(1–2): 165–174.

    Article  PubMed  CAS  Google Scholar 

  44. Frischmeyer PA, van Hoof A, O’Donnell K et al. An mRNA surveillance mechanism that eliminates transcripts lacking termination codons. Science 2002; 295(5563):2258–2261.

    Article  PubMed  CAS  Google Scholar 

  45. Wilson MA, Meaux S, van Hoof A. Diverse aberrancies target yeast mRNAs to cytoplasmic mRNA surveillance pathways. Biochim Biophys Acta. 2008.

    Google Scholar 

  46. Shyu AB, Wilkinson MF, van Hoof A. Messenger RNA regulation: to translate orto degrade. EMBO J 2008; 27(3):471–481.

    Article  PubMed  CAS  Google Scholar 

  47. Amrani N, Jacobson A. All termination events are not equal: Premature termination in yeast is aberrant and triggers NMD. In: Maquat LE, editor. Nonsense-Mediated mRNA decay. georgetown, TX: Landes Bioscience; 2006. p. 15–26.

    Google Scholar 

  48. Maquat LE. NMD in mammalian cells: a history. In: Maquat LE, ed. Nonsense-Mediated mRNA Decay. Georgetown: Landes Bioscience, 2006:43–58.

    Google Scholar 

  49. Baker KE, Parker R. Features of nonsense-mediated mRNA decay. In: Maquat LE, ed. Nonsense-Mediated mRNA Decay. Georgetown: Landes Bioscience, 2006:1–14.

    Google Scholar 

  50. Leeds P, Peltz SW, Jacobson A et al. The product of the yeast UPF1 gene is required for rapid turnover of mRNAs containing a premature translational termination codon. Genes Dev 1991; 5(12A):2303–2314.

    Article  PubMed  CAS  Google Scholar 

  51. Leeds P, Wood JM, Lee BS et al. Gene products that promote mRNA turnover in Saccharomyces cerevisiae. Mol Cell Biol 1992; 12(5):2165–2177.

    PubMed  CAS  Google Scholar 

  52. He F, Jacobson A. Identification of a novel component of the nonsense-mediated mRNA decay pathway by use of an interacting protein screen. Genes Dev 1995; 9(4):437–454.

    Article  PubMed  CAS  Google Scholar 

  53. Cui Y, Hagan KW, Zhang S et al. Identification and characterization of genes that are required for the accelerated degradation of mRNAs containing a premature translational termination codon. Genes Dev 1995; 9(4):423–436.

    Article  PubMed  CAS  Google Scholar 

  54. Lee BS, Culbertson MR. Identification of an additional gene required for eukaryotic nonsense mRNA turnover. Proc Natl Acad Sci USA 1995; 92(22): 10354–10358.

    Article  PubMed  CAS  Google Scholar 

  55. Muhlrad D, Parker R. Premature translational termination triggers mRNA decapping. Nature 1994; 370(6490):578–581.

    Article  PubMed  CAS  Google Scholar 

  56. Takahashi S, Araki Y, Sakuno T et al. Interaction between Ski7p and Upf 1p is required for nonsense-mediated 3′-to-5′ mRNA decay in yeast. EMBO J 2003; 22(15):3951–3959.

    Article  PubMed  CAS  Google Scholar 

  57. Eberle AB, Lykke-Andersen S, Muhlemann O et al. SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells. Nat Struct Mol Biol 2009; 16(1):49–55.

    Article  PubMed  CAS  Google Scholar 

  58. Huntzinger E, Kashima I, Fauser M et al. SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan. RNA. 2008.

    Google Scholar 

  59. Grishok A, Pasquinelli AE, Conte D et al. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 2001; 106(1):23–34.

    Article  PubMed  CAS  Google Scholar 

  60. Hutvagner G, McLachlan J, Pasquinelli AE et al. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 2001; 293(5531):834–838.

    Article  PubMed  CAS  Google Scholar 

  61. Ketting RF, Fischer SE, Bernstein E et al. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 2001; 15(20):2654–2659.

    Article  PubMed  CAS  Google Scholar 

  62. Knight SW, Bass BL. A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science 2001; 293(5538):2269–2271.

    Article  PubMed  CAS  Google Scholar 

  63. Hammond SM, Bernstein E, Beach D et al. An RNA-directed nuclease mediates posttranscriptional gene silencing in Drosophila cells. Nature 2000; 404(6775):293–296.

    Article  PubMed  CAS  Google Scholar 

  64. Hammond SM, Boettcher S, Caudy AA et al. Argonaute2, a link between genetic and biochemical analyses of RNAi. Science 2001; 293(5532): 1146–1150.

    Article  PubMed  CAS  Google Scholar 

  65. Martick M, Horan LH, Noller HF et al. A discontinuous hammerhead ribozyme embedded in a mammalian messenger RNA. Nature 2008; 454(7206):899–902.

    Article  PubMed  CAS  Google Scholar 

  66. Salehi-Ashtiani K, Luptak A, Litovchick A, Szostak JW. A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. Science 2006; 313(5794): 1788–1792.

    Article  PubMed  CAS  Google Scholar 

  67. Webb CH, Riccitelli NJ, Ruminski DJ, Luptak A. Widespread occurrence of self-cleaving ribozymes. Science 2009; 326(5955):953.

    Article  PubMed  CAS  Google Scholar 

  68. Meaux S, van Hoof A. Yeast transcripts cleaved by an internal ribozyme provide new insight into the role of the cap and poly(A) tail in translation and mRNA decay. RNA 2006; 12(7): 1323–1337.

    Article  PubMed  CAS  Google Scholar 

  69. Ball SG, Tirtiaux C, Wickner RB. Genetic Control of L-a and L-(Bc) Dsrna Copy Number in Killer Systems of Saccharomyces cerevisiae. Genetics 1984; 107(2): 199–217.

    PubMed  CAS  Google Scholar 

  70. Ridley SP, Sommer SS, Wickner RB. 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 1984; 4(4):761–770.

    PubMed  CAS  Google Scholar 

  71. Widner WR, Wickner RB. Evidence that the SKI antiviral system of Saccharomyces cerevisiae acts by blocking expression of viral mRNA. Molecular and cellular biology 1993; 13(7):4331–4341.

    PubMed  CAS  Google Scholar 

  72. Masison DC, Blanc A, Ribas JC et al. Decoying the cap-mRNA degradation system by a double-stranded RNA virus and poly(A)-mRNA surveillance by a yeast antiviral system. Mol Cell Biol 1995; 15(5):2763–2771.

    PubMed  CAS  Google Scholar 

  73. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006; 124(4):783–801.

    Article  PubMed  CAS  Google Scholar 

  74. Kawai T, Akira S. Innate immune recognition of viral infection. Nat Immunol 2006; 7(2):131–137.

    Article  PubMed  CAS  Google Scholar 

  75. Pichlmair A, Reis e Sousa C. Innate recognition of viruses. Immunity 2007; 27(3):370–383.

    Article  PubMed  CAS  Google Scholar 

  76. Lu R, Maduro M, Li F et al. Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans. Nature 2005; 436(7053): 1040–1043.

    Article  PubMed  CAS  Google Scholar 

  77. Mourrain P, Beclin C, Elmayan T et al. Arabidopsis SGS2 and SGS3 genes are required for posttranscriptional gene silencing and natural virus resistance. Cell 2000; 101(5):533–542.

    Article  PubMed  CAS  Google Scholar 

  78. Schott DH, Cureton DK, Whelan SP et al. An antiviral role forthe RNA interference machinery in Caenorhabditis elegans. Proc Natl Acad Sci USA 2005; 102(51):18420–18424.

    Article  PubMed  CAS  Google Scholar 

  79. Wilkins C, Dishongh R, Moore SC et al. RNA interference is an antiviral defence mechanism in Caenorhabditis elegans. Nature 2005; 436(7053): 1044–1047.

    Article  PubMed  CAS  Google Scholar 

  80. Hornung V, Ellegast J, Kim S et al. 5′-Triphosphate RNA is the ligand for RIG-I. Science 2006; 314(5801):994–997.

    Article  PubMed  Google Scholar 

  81. Pichlmair A, Schulz O, Tan CP et al. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 2006; 314(5801):997–1001.

    Article  PubMed  CAS  Google Scholar 

  82. Saito T, Owen DM, Jiang F et al. Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA. Nature 2008; 454(7203):523–527.

    Article  PubMed  CAS  Google Scholar 

  83. Weir JR, Bonneau F, Hentschel J, Conti E. Structural analysis reveals the characteristic features of Mtr4, a DExH helicase involved in nuclear RNA processing and surveillance. Proc Natl Acad Sci USA 2010; in press.

    Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology and Molecular Genetics, University of Texas Health Science Center-Houston, Houston, Texas, USA

    Daneen Schaeffer, Amanda Clark, A. Alejandra Klauer, Borislava Tsanova & Ambro van Hoof

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  1. Daneen Schaeffer
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  2. Amanda Clark
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  3. A. Alejandra Klauer
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  4. Borislava Tsanova
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  5. Ambro van Hoof
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  1. Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, Aarhus University, Aarhus, Denmark

    Torben Heick Jensen PhD

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Schaeffer, D., Clark, A., Klauer, A.A., Tsanova, B., van Hoof, A. (2010). Functions of the Cytoplasmic Exosome. In: Jensen, T.H. (eds) RNA Exosome. Advances in Experimental Medicine and Biology, vol 702. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7841-7_7

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