Skip to main content

Thank you for visiting 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.

The enzymes and control of eukaryotic mRNA turnover

The degradation of eukaryotic mRNAs plays important roles in the modulation of gene expression, quality control of mRNA biogenesis and antiviral defenses. In the past five years, many of the enzymes involved in this process have been identified and mechanisms that modulate their activities have begun to be identified. In this review, we describe the enzymes of mRNA degradation and their properties. We highlight that there are a variety of enzymes with different specificities, suggesting that individual nucleases act on distinct subpopulations of transcripts within the cell. In several cases, translation factors that bind mRNA inhibit these nucleases. In addition, recent work has begun to identify distinct mRNP complexes that recruit the nucleases to transcripts through different mRNA-interacting proteins. These properties and complexes suggest multiple mechanisms by which mRNA degradation could be regulated.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1
Figure 2
Figure 3: Models for exosome structure and function.
Figure 4: Eukaryotic decapping enzymes.


  1. 1

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

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2

    Dykxhoorn, D.M., Novina, C.D. & Sharp, P.A. Killing the messenger: short RNAs that silence gene expression. Nat. Rev. Mol. Cell Biol. 4, 457–467 (2003).

    CAS  Google Scholar 

  3. 3

    Maquat, L.E. & Carmichael, G.G. Quality control of mRNA function. Cell 26, 173–176 (2000).

    Google Scholar 

  4. 4

    Tucker, M. & Parker, R. Mechanisms and control of mRNA decapping in Saccharomyces cerevisiae. Annu. Rev. Biochem. 69, 571–595 (2000).

    CAS  PubMed  Google Scholar 

  5. 5

    Mitchell, P. & Tollervey, D. mRNA turnover. Curr. Opin. Cell Biol. 13, 320–325 (2001).

    CAS  PubMed  Google Scholar 

  6. 6

    Anderson, J.S.J. & 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. 17, 1497–1506 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

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

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8

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

    CAS  PubMed  Google Scholar 

  9. 9

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

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Liu, H., Rodgers, N.D., Jiao, X. & Kiledjian, M. The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of pyrophosphatases. EMBO J. 21, 4699–4708 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11

    Dodson, R.E. & Shapiro, D.J. Regulation of pathways of mRNA destabilization and stabilization. Prog. Nucleic Acid Res. Mol. Biol. 72, 129–164 (2002).

    CAS  PubMed  Google Scholar 

  12. 12

    Moore, M.J. Nuclear RNA turnover. Cell 108, 431–434 (2002).

    CAS  PubMed  Google Scholar 

  13. 13

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

    CAS  Google Scholar 

  14. 14

    Cao, D. & Parker, R. Computational modeling and experimental analysis of nonsense-mediated decay in yeast. Cell 113, 533–545 (2003).

    CAS  Google Scholar 

  15. 15

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

    CAS  Google Scholar 

  16. 16

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

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

    CAS  PubMed  Google Scholar 

  18. 18

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19

    Tucker, M. et al. The transcription factor associated proteins Ccr4 and Caf1 are components of the major cytoplasmic mRNA deadenylase in Saccharomyces cerevisiae. Cell 104, 377–386 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Denis, C.L. & Chen, J. The CCR4-NOT complex plays diverse roles in mRNA metabolism. Prog. Nucleic Acid Res. Mol. Biol. 73, 221–250 (2003).

    CAS  PubMed  Google Scholar 

  21. 21

    Dlakic, M. Functionally unrelated signalling proteins contain a fold similar to Mg2+-dependent endonucleases. Trends Biochem. Sci. 25, 272–273 (2000).

    CAS  PubMed  Google Scholar 

  22. 22

    Tucker, M., Staples, R.R., Valencia-Sanchez, M.A., Muhlrad, D. & Parker, R. Ccr4p is the catalytic sub-unit of a Ccr4/Pop2p/Notp mRNA deadenylase complex in Saccharomyces cerevisiae. EMBO J. 21, 1427–1436 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Chen, J., Chiang, Y.C. & Denis, C.L. CCR4, a 3′-5′ poly(A) RNA and ssDNA exonuclease, is the catalytic component of the cytoplasmic deadenylase. EMBO J. 21, 1414–1426 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    Baggs, J.E. & Green, C.B. Nocturnin, a deadenylase in Xenopus laevis retina. A mechanism for posttranscriptional control of circadian-related mRNA. Curr. Biol. 13, 189–198 (2003).

    CAS  PubMed  Google Scholar 

  25. 25

    Daugeron, M.C., Mauxion, F. & Seraphin, B. The yeast POP2 gene encodes a nuclease involved in mRNA deadenylation. Nucleic Acids Res. 29, 2448–2455 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Thore, S., Mauxion, F., Séraphin, B & Suck, D. X-ray structure and activity of the yeast Pop2 protein: a nuclease subunit of the mRNA deadenylase complex. EMBO Rep. 4, 1150–1155 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Moser, M.J., Holley, W.R., Chatterjee, A. & Mian, I.S. The proofreading domain of Escherichia coli DNA polymerase I and other DNA and/or RNA exonuclease domains. Nucleic Acids Res. 25, 5110–5118 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Joyce, C.M. & Steitz, T.A. Polymerase structures and function: variations on a theme? J. Bacteriol. 177, 6321–6329 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Brown, C.E. & Sachs, A.B. Poly(A) tail length control in Saccharomyces cerevisiae occurs by message-specific deadenylation. Mol. Cell. Biol. 18, 6548–6559 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30

    Hammet, A., Pike, B.L. & Heierhorst, J. Posttranscriptional regulation of the RAD5 DNA repair gene by the dun1 kinase and the Pan2-Pan3 poly(A)-nuclease complex contributes to survival of replication blocks. J. Biol. Chem. 277, 22469–22474 (2002).

    CAS  PubMed  Google Scholar 

  31. 31

    Ito, T. et al. A comprehensive two-hybrid analysis to explore the yeast protein interactome. Pro. Natl. Acad. Sci. USA 98, 4277–4278 (2001).

    Google Scholar 

  32. 32

    Åström, J., Åström, A. & Virtanen, A. Properties of a HeLa cell 3′ exonuclease specific for degrading poly(A) tails of mammalian mRNA. J. Biol. Chem. 267, 18154–18159 (1992).

    PubMed  Google Scholar 

  33. 33

    Körner, C.G. & Wahle, E. Poly(A) tail shortening by a mammalian poly(A)-specific 3′-exoribonuclease. J. Biol. Chem. 272, 10448–10456 (1997).

    PubMed  Google Scholar 

  34. 34

    Ren, Y.-G., Martínez, J. & Virtanen, A. Identification of the active site of poly(A)-specific ribonuclease by site-directed mutagenesis and Fe2+-mediated cleavage. J. Biol. Chem. 277, 5982–5987 (2002).

    CAS  PubMed  Google Scholar 

  35. 35

    Lai, W.S., Kennington, E.A. & Blackshear, P.J. Tristetraprolin and its family members can promote the cell-free deadenylation of AU-rich element-containing mRNAs by poly(A) ribonuclease. Mol. Cell. Biol. 23, 3798–3812 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    Gao, M., Fritz, D.T., Ford, L.P. & Wilusz, J. Interaction between a poly(A)-specific ribonuclease and the 5′ cap influences mRNA deadenylation rates in vitro. Mol. Cell 5, 479–488 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Körner, C.G. et al. The deadenylating nuclease (DAN) is involved in poly(A) tail removal during the meiotic maturation of Xenopus oocytes. EMBO J. 17, 5427–5437 (1998).

    PubMed  PubMed Central  Google Scholar 

  38. 38

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39

    Viswanathan, P., Chen, J., Chiang, Y.-C. & Denis, C.L. Identification of multiple RNA features that influence CCR4 deadenylation activity. J. Biol. Chem. 278, 14949–14955 (2003).

    CAS  PubMed  Google Scholar 

  40. 40

    Dehlin, E., Wormington, M., Körner, C.G. & Wahle, E. Cap-dependent deadenylation of mRNA. EMBO J. 19, 1079–1086 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    Martînez, J., Ren, Y.-G., Nilsson, P., Ehrenberg, M. & Virtanen, A. The mRNA cap structure stimulates rate of poly(A) removal and amplifies processivity of degradation. J. Biol. Chem. 276, 27923–27929 (2001).

    PubMed  Google Scholar 

  42. 42

    Sach, A.B. & Deardorff, J.A. Translation initiation requires the PAB-dependent poly(A) ribonuclease in yeast. Cell 70, 961–973 (1992).

    Google Scholar 

  43. 43

    Wickens, M., Bernstein, D.S., Kimble, J. & Parker, R. A PUF family portrait: 3′UTR regulation as a way of life. Trends Genet. 18, 150–157 (2002).

    CAS  PubMed  Google Scholar 

  44. 44

    Mitchell, P. & Tollervey, D. Musing on the structural organization of the exosome complex. Nat. Struct. Biol. 7, 843–846 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45

    Butler, J.S. The yin and yang of the exosome. Trends Cell Biol. 12, 90–96 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47

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

    CAS  PubMed  Google Scholar 

  48. 48

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

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49

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

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    Tanner, N.K. & Linder, P. DExD/H box RNA helicases: from generic motors to specific dissociation functions. Mol. Cell 8, 251–262 (2001).

    CAS  PubMed  Google Scholar 

  52. 52

    Ford, L.P., Watson, J., Keene, J.D. & Wilusz, J. ELAV proteins stabilize deadenylated intermediates in a novel in vitro mRNA deadenylation/degradation system. Genes Dev. 13, 188–201 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54

    Nuss, D.L., Furuichi, Y., Koch, G. & Shatkin, A.J. Detection in HeLa cell extracts of a 7-methyl guanosine specific enzyme activity that cleaves m7GPN. Cell 6, 21–27 (1975).

    CAS  PubMed  Google Scholar 

  55. 55

    Nuss, D.L. & Furuichi, Y. Characterization of the m7G(5')PN-pyrophosphatase activity from HeLa cells. J. Biol. Chem. 252, 2815–2821 (1977).

    CAS  PubMed  Google Scholar 

  56. 56

    Kumagai, H. et al. Purification and properties of a decapping enzyme from rat liver cytosol. Biochim. Biophys. Acta 1119, 45–51 (1992).

    CAS  PubMed  Google Scholar 

  57. 57

    Wang, Z. & Kiledjian, M. The poly(A)-binding protein and an mRNA stability protein jointly regulate an endoribonuclease activity. Mol. Cell. Biol. 20, 6334–6341 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    van Dijk, E., Hir, H.L. & Séraphin, B. DcpS can act in the 5'–3' mRNA decay pathway in addition to the 3'–5' pathway. Proc. Natl. Acad. Sci. USA 100, 12081–12086 (2003).

    CAS  PubMed  Google Scholar 

  59. 59

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

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60

    Beelman, C.A. et al. An essential component of the decapping enzyme required for normal rates of mRNA decay in yeast. Nature 382, 642–646 (1996).

    CAS  Google Scholar 

  61. 61

    Steiger, M., Carr-Schmid, A., Schwartz, D.C., Kiledjian, M. & Parker, R. Analysis of recombinant yeast decapping enzyme. RNA 9, 231–238 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62

    Dunckley, T., Tucker, M. & Parker, R. Two related proteins, Edc1p and Edc2p, stimulate mRNA decapping in Saccharomyces cerevisiae. Genetics 257, 27–37 (2001).

    Google Scholar 

  63. 63

    Lykke-Andersen, J. Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay. Mol. Cell. Biol. 22, 8114–8121 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    Stevens, A. An mRNA decapping enzyme from ribosomes of Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 96, 1150–1055 (1980).

    CAS  PubMed  Google Scholar 

  65. 65

    Wang, Z., Jiao, X., Carr-Schmid, A. & Kiledjian, M. The hDcp2 protein is a mammalian mRNA decapping enzyme. Proc. Natl. Acad. Sci. USA 99, 12663–12668 (2002).

    CAS  PubMed  Google Scholar 

  66. 66

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

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67

    Stevens, A. & Maupin, M.K. A 5′——3′ exoribonuclease of Saccharomyces cerevisiae: size and novel substrate specificity. Arch. Biochem. Biophys. 252, 339–347 (1987).

    CAS  PubMed  Google Scholar 

  68. 68

    Koonin, E.V. A highly conserved sequence motif defining the family of MutT-related proteins from eubacteria, eukaryotes and viruses. Nucleic Acids Res. 21, 4847 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. 69

    Bessman, M.J., Frick, D.N. & O'Handley, S.F. The MutT proteins or 'Nudix' hydrolases, a family of versatile, widely distributed, 'housecleaning' enzymes. J. Biol. Chem. 271, 25059–25062 (1996).

    CAS  Google Scholar 

  70. 70

    Callebaut, I. An EVH1/WH1 domain as a key actor in TGFB signalling. FEBS Lett. 519, 178–180 (2002).

    CAS  PubMed  Google Scholar 

  71. 71

    She, M. et al. Crystal structure of Dcp1p and its functional implications in mRNA Decapping Nat. Struct. Mol. Biol. (in the press).

  72. 72

    Ball, L.J., Jarchau, T., Oschkinat, H. & Walter, U. EVH1 domains: structure, function and interactions. FEBS Lett. 513, 45–52 (2002).

    CAS  PubMed  Google Scholar 

  73. 73

    Piccirillo, C., Khanna, R. & Kiledjian, M. Functional characterization of the mammalian mRNA decapping enzyme hDcp2. RNA 9, 1138–1147 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74

    LaGrandeur, T.E. & Parker, R. Isolation and characterization of Dcp1p, the yeast mRNA decapping enzyme. EMBO J. 17, 1487–1496 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. 75

    Caponigro, G. & Parker, R. Multiple functions of the poly(A) binding protein in mRNA decapping and deadenylation. Genes Dev. 9, 2421–2432 (1995).

    CAS  Google Scholar 

  76. 76

    Coller, J.M., Gray, N.K. & Wickens, M.P. mRNA stabilization by poly(A) binding protein is independent of poly(A) and requires translation. Genes Dev. 12, 3226–3235 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. 77

    Wilusz, C.J. et al. Poly(A)-binding proteins regulate both mRNA deadenylation and decapping in yeast cytoplasmic extracts. RNA 7, 1416–1424 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Tarun, S.Z. Jr. & Sachs, A.B. Association of the yeast poly(A) tail binding protein with translation initiation factor eIF-4G. EMBO J. 16, 7168–7177 (1996).

    Google Scholar 

  79. 79

    Schwartz, D. & Parker, R. Mutations in translation initiation factors lead to increased rates of deadenylation and decapping of yeast mRNAs. Mol. Cell. Biol. 19, 5247–5256 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80

    Schwartz, D. & Parker, R. mRNA decapping in yeast requires dissociation of the cap binding protein, eukaryotic translation initiation factor 4E. Mol. Cell. Biol. 20, 7933–7942 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. 81

    Khanna, R. & Kiledjian, M. Poly(A)-binding protein mediated regulation of hDcp2 decapping. Genes Dev. (2004, in press).

  82. 82

    Wang, Z., Day, N., Trifillis, P. & Kiledjian, M. An mRNA stability complex functions with poly(A)-binding protein to stabilize mRNA in vitro. Mol. Cell. Biol. 19, 4552–4560 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. 83

    Vilela, C., Velasco, C., Ptushkina, M. & McCarthy, J.E. . The eukaryotic mRNA decapping protein Dcp1 interacts physically and functionally with the eIF4F translation initiation complex. EMBO J. 19, 4372–4382 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84

    Tharun, S. & Parker, R. Targeting an mRNA for decapping: displacement of translation factors and association of the Lsm1p-7p complex on deadenylated yeast mRNAs. Mol. Cell 8, 1075–1083 (2001).

    CAS  PubMed  Google Scholar 

  85. 85

    Sheth, U.R. & Parker, R. Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science 300, 805–808 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 86

    Ingelfinger, D., Arndt-Jovin, D.J., Luhrmann, R. & Achset, T. The human LSm1-7 proteins colocalize with the mRNA-degrading enzymes Dcp1/2 and Xrn1 in distinct cytoplasmic foci. RNA 8, 1489–1501 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. 87

    Bashkirov, V.I., Scherthan, H., Solinger, J.A., Buerstedde, J.M. & Heyer, W.D. A mouse cytoplasmic exoribonuclease (mXRN1p) with preference for G4 tetraplex substrates. J. Cell Biol. 136, 761–773 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. 88

    Beelman, C.A. & Parker, R. Differential effects of translational inhibition in cis and in trans on the decay of the unstable yeast MFA2 mRNA. J. Biol. Chem. 269, 9687–9692 (1994).

    CAS  Google Scholar 

  89. 89

    Boeck, R., Lapeyre, P., Brown, C.E. & Sachs, A.B. Capped mRNA degradation intermediates accumulate in the yeast spb8-2 mutant. Mol. Cell. Biol. 18, 5062–5072 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90

    Tharun, S. et al. Yeast Sm-like proteins function in mRNA decapping and decay. Nature 404, 515–518 (2000).

    CAS  Google Scholar 

  91. 91

    Bouveret, E., Rigaut, G., Shevchenko, A., Wilm, M. & Seraphin, B. A Sm-like protein complex that participates in mRNA degradation. EMBO J. 19, 1661–1671 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92

    Bonnerot, C., Boeck, R. & Lapeyre, B. The two proteins Pat1p (Mrt1p) and Spb8p interact in vivo, are required for mRNA decay, and are functionally linked to Pab1p. Mol. Cell. Biol. 20, 5939–5946 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93

    Coller, J.M., Tucker, M., Sheth, U., Valencia-Sanchez, M.A. & Parker, R. The DEAD box helicase, Dhh1p, functions in mRNA decapping and interacts with both the decapping and deadenylase complexes. RNA 7, 1717–1727 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94

    Fischer, N. & Weis, K. The DEAD box protein Dhh1 stimulates the decapping enzyme Dcp1. EMBO J. 21, 2788–2797 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 95

    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. 9, 437–454 (1995).

    CAS  PubMed  Google Scholar 

  96. 96

    Kshirsagar, M. & Parker, R. Edc3p, a novel conserved protein, enhances mRNA decay in Yeast. Genetics (in the press).

  97. 97

    Schwartz, D., Decker, C.J. & Parker, R. The enhancer of decapping proteins, Edc1p and Edc2p, bind RNA and stimulate activity of the decapping enzyme. RNA 9, 239–251 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. 98

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

    CAS  PubMed  PubMed Central  Google Scholar 

  99. 99

    Zuk, D. & Jacobson, A. A single amino acid substitution in yeast eIF5A results in mRNA stabilization. EMBO J. 17, 2914–2925 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. 100

    Till, D.D., et al. Identification and developmental expression of a 5′-3′ exoribonuclease from Drosophila melanogaster. Mech. Dev. 79, 51–55 (1998).

    CAS  PubMed  Google Scholar 

  101. 101

    Zhang, W., Williams, C.J., Hagan, K. & Peltz, S.W. Mutations in VPS16 and MRT1 stabilize mRNAs by activating an inhibitor of the decapping enzyme. Mol. Cell. Biol. 19, 7568–7576 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. 102

    Zuk, D., Belk, J.P. & Jacobson, A. Temperature-sensitive mutations in the Saccharomyces cerevisiae MRT4, GRC5, SLA2 and THS1 genes result in defects in mRNA turnover. Genetics 153, 35–47 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. 103

    Uetz, P. et al. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 403, 623–627 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. 104

    Fromont-Racine, M. et al. Genome-wide protein interaction screens reveal functional networds involving Sm-like proteins. Yeast 17, 95–110 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. 105

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

    CAS  Google Scholar 

Download references

Author information



Corresponding authors

Correspondence to Roy Parker or Haiwei Song.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Parker, R., Song, H. The enzymes and control of eukaryotic mRNA turnover. Nat Struct Mol Biol 11, 121–127 (2004).

Download citation

Further reading


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