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.

Structural and molecular mechanisms for the control of eukaryotic 5′–3′ mRNA decay

Nature Structural & Molecular Biology volume 25, pages 1077–1085 (2018)Cite this article

Subjects

A Publisher Correction to this article was published on 21 December 2018

This article has been updated

Abstract

5′–3′ RNA decay pathways are critical for quality control and regulation of gene expression. Structural and biochemical studies have provided insights into the key nucleases that carry out deadenylation, decapping, and exonucleolysis during 5′–3′ decay, but detailed understanding of how these activities are coordinated is only beginning to emerge. Here we review recent mechanistic insights into the control of 5′–3′ RNA decay, including coupling between translation and decay, coordination between the complexes and activities that process 5′ and 3′ RNA termini, conformational control of enzymatic activity, liquid phase separation, and RNA modifications.

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

Fig. 1: Overview of the major steps in the 5′–3′ mRNA decay pathway.
Fig. 2: Codon optimality couples translation elongation and mRNA decay.
Fig. 3: Models for the recruitment and action of PAN2–PAN3 and CCR4–NOT 3′ deadenylase complexes.
Fig. 4: Protein–protein interactions that link 3′ end deadenylation to 5′ end decay.
Fig. 5: Control of mRNA decapping by conformational change, protein–protein interactions, and autoinhibition.

Change history

  • 21 December 2018

    The original and corrected figures are shown in the accompanying Publisher Correction.

References

  1. Zinder, J. C. & Lima, C. D. Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors. Genes Dev. 31, 88–100 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Schmidt, C. et al. The cryo-EM structure of a ribosome-Ski2-Ski3-Ski8 helicase complex. Science 354, 1431–1433 (2016).

    CAS  PubMed  Google Scholar 

  3. Despic, V. & Neugebauer, K. M. RNA tales - how embryos read and discard messages from mom. J. Cell Sci. 131, jcs201996 (2018).

    PubMed  Google Scholar 

  4. Chen, C.-Y. A. & Shyu, A.-B. AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem. Sci. 20, 465–470 (1995).

    CAS  PubMed  Google Scholar 

  5. Li, Y., Dai, J., Song, M., Fitzgerald-Bocarsly, P. & Kiledjian, M. Dcp2 decapping protein modulates mRNA stability of the critical interferon regulatory factor (IRF) IRF-7. Mol. Cell. Biol. 32, 1164–1172 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Abernathy, E. & Glaunsinger, B. Emerging roles for RNA degradation in viral replication and antiviral defense. Virology 479-480, 600–608 (2015).

    CAS  PubMed  Google Scholar 

  7. Lykke-Andersen, S. & Jensen, T. H. Nonsense-mediated mRNA decay: an intricate machinery that shapes transcriptomes. Nat. Rev. Mol. Cell Biol. 16, 665–677 (2015).

    CAS  PubMed  Google Scholar 

  8. Moore, M. J. From birth to death: the complex lives of eukaryotic mRNAs. Science 309, 1514–1518 (2005).

    CAS  PubMed  Google Scholar 

  9. Parker, R. RNA degradation in Saccharomyces cerevisae. Genetics 191, 671–702 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Brannan, K. et al. mRNA decapping factors and the exonuclease Xrn2 function in widespread premature termination of RNA polymerase II transcription. Mol. Cell 46, 311–324 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Hu, W., Sweet, T. J., Chamnongpol, S., Baker, K. E. & Coller, J. Co-translational mRNA decay in Saccharomyces cerevisiae. Nature 461, 225–229 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  13. Karousis, E. D., Nasif, S. & Mühlemann, O. Nonsense-mediated mRNA decay: novel mechanistic insights and biological impact. Wiley Interdiscip. Rev. RNA 7, 661–682 (2016).

    CAS  PubMed  Google Scholar 

  14. Jonas, S. & Izaurralde, E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat. Rev. Genet. 16, 421–433 (2015).

    CAS  PubMed  Google Scholar 

  15. Barreau, C., Paillard, L. & Osborne, H. B. AU-rich elements and associated factors: are there unifying principles? Nucleic Acids Res. 33, 7138–7150 (2006).

    PubMed  PubMed Central  Google Scholar 

  16. Radhakrishnan, A. & Green, R. Connections underlying translation and mRNA stability. J. Mol. Biol. 428, 3558–3564 (2016).

    CAS  PubMed  Google Scholar 

  17. Yu, X., Willmann, M. R., Anderson, S. J. & Gregory, B. D. Genome-wide mapping of uncapped and cleaved transcripts reveals a role for the nuclear mRNA cap-binding complex in cotranslational RNA decay in Arabidopsis. Plant Cell 28, 2385–2397 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Tat, T. T., Maroney, P. A., Chamnongpol, S., Coller, J. & Nilsen, T. W. Cotranslational microRNA mediated messenger RNA destabilization. eLife 5, e12880, https://doi.org/10.7554/eLife.12880 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pelechano, V., Wei, W. & Steinmetz, L. M. Widespread co-translational RNA decay reveals ribosome dynamics. Cell 161, 1400–1412 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Coller, J. & Parker, R. Eukaryotic mRNA decapping. Annu. Rev. Biochem. 73, 861–890 (2004).

    CAS  PubMed  Google Scholar 

  21. Caponigro, G., Muhlrad, D. & Parker, R. A small segment of the MAT alpha 1 transcript promotes mRNA decay in Saccharomyces cerevisiae: a stimulatory role for rare codons. Mol. Cell. Biol. 13, 5141–5148 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Presnyak, V. et al. Codon optimality is a major determinant of mRNA stability. Cell 160, 1111–1124 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Mishima, Y. & Tomari, Y. Codon usage and 3′ UTR length determine maternal mRNA stability in zebrafish. Mol. Cell 61, 874–885 (2016).

    CAS  PubMed  Google Scholar 

  24. Bazzini, A. A. et al. Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition. EMBO J. 35, 2087–2103 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Harigaya, Y. & Parker, R. Analysis of the association between codon optimality and mRNA stability in Schizosaccharomyces pombe. BMC Genomics 17, 895 (2016).

    PubMed  PubMed Central  Google Scholar 

  26. Jeacock, L., Faria, J. & Horn, D. Codon usage bias controls mRNA and protein abundance in trypanosomatids. eLife 7, e32496 (2018).

    PubMed  PubMed Central  Google Scholar 

  27. Presnyak, V. & Coller, J. The DHH1/RCKp54 family of helicases: an ancient family of proteins that promote translational silencing. Biochim. Biophys. Acta 1829, 817–823 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Radhakrishnan, A. et al. The DEAD-box protein Dhh1p couples mRNA decay and translation by monitoring codon optimality. Cell 167, 122–132.e9 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Wiederhold, K. & Passmore, L. A. Cytoplasmic deadenylation: regulation of mRNA fate. Biochem. Soc. Trans. 38, 1531–1536 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Smith, R. W. P., Blee, T. K. P. & Gray, N. K. Poly(A)-binding proteins are required for diverse biological processes in metazoans. Biochem. Soc. Trans. 42, 1229–1237 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Wolf, J. & Passmore, L. A. mRNA deadenylation by Pan2-Pan3. Biochem. Soc. Trans. 42, 184–187 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Collart, M. A. The Ccr4-Not complex is a key regulator of eukaryotic gene expression. Wiley Interdiscip. Rev. RNA 7, 438–454 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Webster, M. W. et al. mRNA deadenylation is coupled to translation rates by the differential activities of Ccr4-Not nucleases. Mol. Cell 70, 1089–1100.e8 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Sun, M. et al. Global analysis of eukaryotic mRNA degradation reveals Xrn1-dependent buffering of transcript levels. Mol. Cell 52, 52–62 (2013).

    CAS  PubMed  Google Scholar 

  35. Jonas, S. et al. An asymmetric PAN3 dimer recruits a single PAN2 exonuclease to mediate mRNA deadenylation and decay. Nat. Struct. Mol. Biol. 21, 599–608 (2014).

    CAS  PubMed  Google Scholar 

  36. Schäfer, I. B., Rode, M., Bonneau, F., Schüssler, S. & Conti, E. The structure of the Pan2-Pan3 core complex reveals cross-talk between deadenylase and pseudokinase. Nat. Struct. Mol. Biol. 21, 591–598 (2014).

    PubMed  Google Scholar 

  37. Wolf, J. et al. Structural basis for Pan3 binding to Pan2 and its function in mRNA recruitment and deadenylation. EMBO J. 33, 1514–1526 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  39. Uchida, N., Hoshino, S. & Katada, T. Identification of a human cytoplasmic poly(A) nuclease complex stimulated by poly(A)-binding protein. J. Biol. Chem. 279, 1383–1391 (2004).

    CAS  PubMed  Google Scholar 

  40. Braun, J. E., Huntzinger, E., Fauser, M. & Izaurralde, E. GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets. Mol. Cell 44, 120–133 (2011).

    CAS  PubMed  Google Scholar 

  41. Ukleja, M. et al. The architecture of the Schizosaccharomyces pombe CCR4-NOT complex. Nat. Commun. 7, 10433 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Stowell, J. A. W. et al. Reconstitution of targeted deadenylation by the Ccr4-Not complex and the YTH domain protein Mmi1. Cell Rep. 17, 1978–1989 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Fabian, M. R. et al. Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin. Nat. Struct. Mol. Biol. 20, 735–739 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Mauxion, F., Chen, C.-Y. A., Séraphin, B. & Shyu, A.-B. BTG/TOB factors impact deadenylases. Trends Biochem. Sci. 34, 640–647 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Chen, Y. et al. A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal direct links between miRNA target recognition and silencing. Mol. Cell 54, 737–750 (2014).

    CAS  PubMed  Google Scholar 

  46. Fabian, M. R. et al. miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT. Nat. Struct. Mol. Biol. 18, 1211–1217 (2011).

    CAS  PubMed  Google Scholar 

  47. Raisch, T. et al. Distinct modes of recruitment of the CCR4-NOT complex by Drosophila and vertebrate Nanos. EMBO J. 35, 974–990 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Sgromo, A. et al. Drosophila Bag-of-marbles directly interacts with the CAF40 subunit of the CCR4-NOT complex to elicit repression of mRNA targets. RNA 24, 381–395 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Amaya Ramirez, C. C., Hubbe, P., Mandel, N. & Béthune, J. 4EHP-independent repression of endogenous mRNAs by the RNA-binding protein GIGYF2. Nucleic Acids Res. 46, 5792–5808 (2018).

    PubMed  PubMed Central  Google Scholar 

  50. Loh, B., Jonas, S. & Izaurralde, E. The SMG5-SMG7 heterodimer directly recruits the CCR4-NOT deadenylase complex to mRNAs containing nonsense codons via interaction with POP2. Genes Dev. 27, 2125–2138 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Yi, H. et al. PABP cooperates with the CCR4-NOT complex to promote mRNA deadenylation and block precocious decay. Mol. Cell 70, 1081–1088.e5 (2018).

    CAS  PubMed  Google Scholar 

  52. Lima, S. A. et al. Short poly(A) tails are a conserved feature of highly expressed genes. Nat. Struct. Mol. Biol. 24, 1057–1063 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Jonas, S. & Izaurralde, E. The role of disordered protein regions in the assembly of decapping complexes and RNP granules. Genes Dev. 27, 2628–2641 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Chowdhury, A., Mukhopadhyay, J. & Tharun, S. The decapping activator Lsm1p-7p-Pat1p complex has the intrinsic ability to distinguish between oligoadenylated and polyadenylated RNAs. RNA 13, 998–1016 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Charenton, C. et al. A unique surface on Pat1 C-terminal domain directly interacts with Dcp2 decapping enzyme and Xrn1 5′-3′ mRNA exonuclease in yeast. Proc. Natl Acad. Sci. USA 114, E9493–E9501 (2017).

    CAS  PubMed  Google Scholar 

  56. Wu, D. et al. Lsm2 and Lsm3 bridge the interaction of the Lsm1-7 complex with Pat1 for decapping activation. Cell Res. 24, 233–246 (2014).

    CAS  PubMed  Google Scholar 

  57. Chang, H., Lim, J., Ha, M. & Kim, V. N. TAIL-seq: genome-wide determination of poly(A) tail length and 3′ end modifications. Mol. Cell 53, 1044–1052 (2014).

    CAS  PubMed  Google Scholar 

  58. De Almeida, C., Scheer, H., Zuber, H. & Gagliardi, D. RNA uridylation: a key posttranscriptional modification shaping the coding and noncoding transcriptome. Wiley Interdiscip. Rev. RNA 9, e1440 (2018).

    Google Scholar 

  59. Rissland, O. S. & Norbury, C. J. Decapping is preceded by 3′ uridylation in a novel pathway of bulk mRNA turnover. Nat. Struct. Mol. Biol. 16, 616–623 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Song, M.-G. & Kiledjian, M. 3′ Terminal oligo U-tract-mediated stimulation of decapping. RNA 13, 2356–2365 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Sharif, H. et al. Structural analysis of the yeast Dhh1-Pat1 complex reveals how Dhh1 engages Pat1, Edc3 and RNA in mutually exclusive interactions. Nucleic Acids Res. 41, 8377–8390 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Fromm, S. A. et al. The structural basis of Edc3- and Scd6-mediated activation of the Dcp1:Dcp2 mRNA decapping complex. EMBO J. 31, 279–290 (2012).

    CAS  PubMed  Google Scholar 

  63. Badis, G., Saveanu, C., Fromont-Racine, M. & Jacquier, A. Targeted mRNA degradation by deadenylation-independent decapping. Mol. Cell 15, 5–15 (2004).

    CAS  PubMed  Google Scholar 

  64. He, F., Li, C., Roy, B. & Jacobson, A. Yeast Edc3 targets RPS28B mRNA for decapping by binding to a 3′ untranslated region decay-inducing regulatory element. Mol. Cell. Biol. 34, 1438–1451 (2014).

    PubMed  PubMed Central  Google Scholar 

  65. Jacobson, A., He, F. & Celik, A. General decapping activators target different subsets of inefficiently translated mRNAs. Preprint at bioRxiv https://doi.org/10.1101/344937 (2018).

  66. Ozgur, S. et al. Structure of a human 4E-T/DDX6/CNOT1 complex reveals the different interplay of DDX6-binding proteins with the CCR4-NOT complex. Cell Rep. 13, 703–711 (2015).

    CAS  PubMed  Google Scholar 

  67. Duchaine, T. F. & Fabian, M. R. Mechanistic insights into microRNA-mediated gene silencing. Cold Spring Harb. Perspect. Biol. 032771, a032771 (2018).

    Google Scholar 

  68. Adivarahan, S. et al. Spatial organization of single mRNPs at different stages of the gene expression pathway. Mol. Cell. https://doi.org/10.1016/j.molcel.2018.10.010 (2018).

  69. Chang, C.-T., Bercovich, N., Loh, B., Jonas, S. & Izaurralde, E. The activation of the decapping enzyme DCP2 by DCP1 occurs on the EDC4 scaffold and involves a conserved loop in DCP1. Nucleic Acids Res. 42, 5217–5233 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Grudzien-Nogalska, E. & Kiledjian, M. New insights into decapping enzymes and selective mRNA decay. Wiley Interdiscip. Rev. RNA 8, e1379 (2017).

    Google Scholar 

  71. Kiledjian, M. Eukaryotic RNA 5′-end NAD+ capping and deNADding. Trends Cell Biol. 28, 454–464 (2018).

    CAS  PubMed  Google Scholar 

  72. Arribas-Layton, M., Wu, D., Lykke-Andersen, J. & Song, H. Structural and functional control of the eukaryotic mRNA decapping machinery. Biochim. Biophys. Acta 1829, 580–589 (2013).

    CAS  PubMed  Google Scholar 

  73. Floor, S. N., Borja, M. S. & Gross, J. D. Interdomain dynamics and coactivation of the mRNA decapping enzyme Dcp2 are mediated by a gatekeeper tryptophan. Proc. Natl Acad. Sci. USA 109, 2872–2877 (2012).

    CAS  PubMed  Google Scholar 

  74. Wurm, J. P., Holdermann, I., Overbeck, J. H., Mayer, P. H. O. & Sprangers, R. Changes in conformational equilibria regulate the activity of the Dcp2 decapping enzyme. Proc. Natl Acad. Sci. USA 114, 6034–6039 (2017).

    CAS  PubMed  Google Scholar 

  75. He, F. & Jacobson, A. Control of mRNA decapping by positive and negative regulatory elements in the Dcp2 C-terminal domain. RNA 21, 1633–1647, https://doi.org/10.1261/rna.052449.115 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Borja, M. S., Piotukh, K., Freund, C. & Gross, J. D. Dcp1 links coactivators of mRNA decapping to Dcp2 by proline recognition. RNA 17, 278–290 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Kolesnikova, O., Back, R., Graille, M. & Séraphin, B. Identification of the Rps28 binding motif from yeast Edc3 involved in the autoregulatory feedback loop controlling RPS28B mRNA decay. Nucleic Acids Res. 41, 9514–9523 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Eulalio, A. et al. Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing. Genes Dev. 21, 2558–2570 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Sharif, H. & Conti, E. Architecture of the Lsm1-7-Pat1 complex: a conserved assembly in eukaryotic mRNA turnover. Cell Rep. 5, 283–291 (2013).

    CAS  PubMed  Google Scholar 

  80. Nissan, T., Rajyaguru, P., She, M., Song, H. & Parker, R. Decapping activators in Saccharomyces cerevisiae act by multiple mechanisms. Mol. Cell 39, 773–783 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Lai, T. et al. Structural basis of the PNRC2-mediated link between mrna surveillance and decapping. Structure 20, 2025–2037 (2012).

    CAS  PubMed  Google Scholar 

  82. Mugridge, J. S., Ziemniak, M., Jemielity, J. & Gross, J. D. Structural basis of mRNA-cap recognition by Dcp1-Dcp2. Nat. Struct. Mol. Biol. 23, 987–994 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Nicholson, P., Gkratsou, A., Josi, C., Colombo, M. & Mühlemann, O. Dissecting the functions of SMG5, SMG7, and PNRC2 in nonsense-mediated mRNA decay of human cells. RNA 24, 557–573 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Cho, H., Kim, K. M. & Kim, Y. K. Human proline-rich nuclear receptor coregulatory protein 2 mediates an interaction between mRNA surveillance machinery and decapping complex. Mol. Cell 33, 75–86 (2009).

    CAS  PubMed  Google Scholar 

  85. Mugridge, J. S., Tibble, R. W., Ziemniak, M., Jemielity, J. & Gross, J. D. Structure of the activated Edc1-Dcp1-Dcp2-Edc3 mRNA decapping complex with substrate analog poised for catalysis. Nat. Commun. 9, 1152 (2018).

    PubMed  PubMed Central  Google Scholar 

  86. Charenton, C. et al. Structure of the active form of Dcp1-Dcp2 decapping enzyme bound to m7GDP and its Edc3 activator. Nat. Struct. Mol. Biol. 23, 982–986 (2016).

    CAS  PubMed  Google Scholar 

  87. She, M. et al. Structural basis of dcp2 recognition and activation by dcp1. Mol. Cell 29, 337–349 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Deshmukh, M. V. et al. mRNA decapping is promoted by an RNA-binding channel in Dcp2. Mol. Cell 29, 324–336 (2008).

    CAS  PubMed  Google Scholar 

  89. Tharun, S. & Parker, R. Analysis of mutations in the yeast mRNA decapping enzyme. Genetics 151, 1273–1285 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Valkov, E. et al. Structure of the Dcp2-Dcp1 mRNA-decapping complex in the activated conformation. Nat. Struct. Mol. Biol. 23, 574–579 (2016).

    CAS  PubMed  Google Scholar 

  91. Valkov, E., Jonas, S. & Weichenrieder, O. Mille viae in eukaryotic mRNA decapping. Curr. Opin. Struct. Biol. 47, 40–51 (2017).

    CAS  PubMed  Google Scholar 

  92. Paquette, D. R., Tibble, R. W., Daifuku, T. S. & Gross, J. D. Control of mRNA decapping by autoinhibition. Nucleic Acids Res. 46, 6318–6329 (2018).

    PubMed  PubMed Central  Google Scholar 

  93. Nagarajan, V. K., Jones, C. I., Newbury, S. F. & Green, P. J. XRN 5′→3′ exoribonucleases: structure, mechanisms and functions. Biochim. Biophys. Acta 1829, 590–603 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Tuck, A. C. & Tollervey, D. A transcriptome-wide atlas of RNP composition reveals diverse classes of mRNAs and lncRNAs. Cell 154, 996–1009 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Boeynaems, S. et al. Protein phase separation: a new phase in cell biology. Trends Cell Biol. 28, 420–435 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18, 285–298 (2017).

    CAS  PubMed  Google Scholar 

  97. Parker, R. & Sheth, U. P bodies and the control of mRNA translation and degradation. Mol. Cell 25, 635–646 (2007).

    CAS  PubMed  Google Scholar 

  98. Luo, Y., Na, Z. & Slavoff, S. A. P-Bodies: Composition, Properties, and Functions. Biochemistry 57, 2424–2431 (2018).

    CAS  PubMed  Google Scholar 

  99. Eulalio, A., Behm-Ansmant, I., Schweizer, D. & Izaurralde, E. P-body formation is a consequence, not the cause, of RNA-mediated gene silencing. Mol. Cell. Biol. 27, 3970–3981 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Chan, L. Y., Mugler, C. F., Heinrich, S., Vallotton, P. & Weis, K. Non-invasive measurement of mRNA decay reveals translation initiation as the major determinant of mRNA stability. eLife 7, e32536 (2018).

    PubMed  PubMed Central  Google Scholar 

  101. Sheu-Gruttadauria, J. & MacRae, I. J. Phase transitions in the assembly and function of human miRISC. Cell 173, 946–957.e16 (2018).

    CAS  PubMed  Google Scholar 

  102. Hubstenberger, A. et al. P-body purification reveals the condensation of repressed mRNA regulons. Mol. Cell 68, 144–157.e5 (2017).

    CAS  PubMed  Google Scholar 

  103. Horvathova, I. et al. The dynamics of mRNA turnover revealed by single-molecule imaging in single cells. Mol. Cell 68, 615–625.e9 (2017).

    CAS  PubMed  Google Scholar 

  104. Tutucci, E. et al. An improved MS2 system for accurate reporting of the mRNA life cycle. Nat. Methods 15, 81–89 (2018).

    CAS  PubMed  Google Scholar 

  105. Fromm, S. A. et al. In vitro reconstitution of a cellular phase-transition process that involves the mRNA decapping machinery. Angew. Chem. Int. Ed. Engl. 53, 7354–7359 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Schütz, S., Nöldeke, E. R. & Sprangers, R. A synergistic network of interactions promotes the formation of in vitro processing bodies and protects mRNA against decapping. Nucleic Acids Res. 45, 6911–6922 (2017).

    PubMed  PubMed Central  Google Scholar 

  107. Wang, C. et al. Context-dependent deposition and regulation of mRNAs in P-bodies. eLife 7, e29815 (2018).

    PubMed  PubMed Central  Google Scholar 

  108. Roundtree, I. A., Evans, M. E., Pan, T. & He, C. Dynamic RNA modifications in gene expression regulation. Cell 169, 1187–1200 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Fu, Y., Dominissini, D., Rechavi, G. & He, C. Gene expression regulation mediated through reversible m6A RNA methylation. Nat. Rev. Genet. 15, 293–306 (2014).

    CAS  PubMed  Google Scholar 

  110. Mauer, J. et al. Reversible methylation of m6Am in the 5′ cap controls mRNA stability. Nature 541, 371–375 (2017).

    CAS  PubMed  Google Scholar 

  111. Meyer, K. D. & Jaffrey, S. R. Rethinking m6A readers, writers, and erasers. Annu. Rev. Cell Dev. Biol. 33, 319–342 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Luo, S. & Tong, L. Molecular basis for the recognition of methylated adenines in RNA by the eukaryotic YTH domain. Proc. Natl Acad. Sci. USA 111, 13834–13839 (2014).

    CAS  PubMed  Google Scholar 

  113. Wang, X. et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 505, 117–120 (2014).

    PubMed  Google Scholar 

  114. Du, H. et al. YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nat. Commun. 7, 12626 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Kretschmer, J. et al. The m6A reader protein YTHDC2 interacts with the small ribosomal subunit and the 5′-3′ exoribonuclease XRN1. RNA 24, 1339–1350 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Huang, H. et al. Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat. Cell Biol. 20, 285–295 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Slobodin, B. et al. Transcription impacts the efficiency of mRNA translation via co-transcriptional N6-adenosine methylation. Cell 169, 326–337.e12 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Choi, J. et al. 2′-O-methylation in mRNA disrupts tRNA decoding during translation elongation. Nat. Struct. Mol. Biol. 25, 208–216 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

J.D.G. and J.S.M. acknowledge grant support from NIH RO1 RM078360 and F32 GM105313. J.C. acknowledges grant support from NIH RO1 GM118018 and GM125086. We thank members of the Gross and Coller labs for helpful comments on the manuscript.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA

    Jeffrey S. Mugridge & John D. Gross

  2. The Center for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH, USA

    Jeff Coller

Authors
  1. Jeffrey S. Mugridge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeff Coller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John D. Gross
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John D. Gross.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mugridge, J.S., Coller, J. & Gross, J.D. Structural and molecular mechanisms for the control of eukaryotic 5′–3′ mRNA decay. Nat Struct Mol Biol 25, 1077–1085 (2018). https://doi.org/10.1038/s41594-018-0164-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41594-018-0164-z

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