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All things must pass: contrasts and commonalities in eukaryotic and bacterial mRNA decay

Nature Reviews Molecular Cell Biology volume 11, pages 467–478 (2010)Cite this article

Subjects

Key Points

  • Bacterial and eukaryotic mRNAs differ markedly in their structure and organization and in the means by which they recruit ribosomes for translation. Early evidence led to the conclusion that the principal mechanisms of mRNA degradation in these organisms are also different, as mRNA lifetimes seemed to be controlled primarily by internal events (endonucleolytic cleavage) in bacteria and by 3′- and 5′-terminal events (deadenylation, decapping and exonucleolytic digestion) in eukaryotic cells.

  • Subsequent discoveries have identified several striking parallels between the mechanisms by which mRNA is degraded in bacteria and eukaryotes. These include the triggering of bacterial mRNA degradation by a 5′-terminal event (pyrophosphate removal) that resembles eukaryotic decapping, roles for 3′ polyadenylation and 5′ exonucleolytic digestion in both bacterial and eukaryotic RNA turnover, and the importance of internal cleavage for the decay of certain eukaryotic mRNAs. Furthermore, some key degradative enzymes in these two kingdoms seem to have evolved from a common ancestor, suggesting that they have an ancient role in RNA degradation.

  • All organisms seem to have quality control pathways for rapidly destroying defective mRNAs that cannot be translated properly. Despite similar outcomes, the mechanisms of mRNA degradation through these pathways differ substantially between bacteria and eukaryotes.

  • Both bacteria and eukaryotes use short non-coding RNAs (sRNAs in bacteria and microRNAs or small interfering RNAs in eukaryotes) to regulate gene expression. In each cell type, base pairing of the non-coding RNA to a partially or fully complementary mRNA generally leads to translational repression and accelerated mRNA decay. The principal mechanisms by which non-coding RNAs cause these effects in bacteria and eukaryotes seem to differ in several ways. Nevertheless, recent evidence suggests that a distinct class of non-coding RNAs (CRISPR RNAs) may trigger mRNA degradation in some bacterial species by a mechanism reminiscent of RNA interference in eukaryotes.

  • Despite growing recognition of the similarities between mRNA degradation in bacteria and eukaryotic cells, some fundamental differences remain. Foremost among these is the widespread importance of low-specificity endonucleases in bacterial mRNA decay and their much more limited role in eukaryotes, where mRNA degradation is dominated by events at the 3′ and 5′ termini. This difference may be an evolutionary consequence of the distinct mechanisms by which bacteria and eukaryotes control translation initiation.

Abstract

Despite its universal importance for controlling gene expression, mRNA degradation was initially thought to occur by disparate mechanisms in eukaryotes and bacteria. This conclusion was based on differences in the structures used by these organisms to protect mRNA termini and in the RNases and modifying enzymes originally implicated in mRNA decay. Subsequent discoveries have identified several striking parallels between the cellular factors and molecular events that govern mRNA degradation in these two kingdoms of life. Nevertheless, some key distinctions remain, the most fundamental of which may be related to the different mechanisms by which eukaryotes and bacteria control translation initiation.

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Figure 1: Differences in the structure and translation of bacterial and eukaryotic mRNAs.
Figure 2: Conventional pathways for mRNA degradation in E. coli and eukaryotic cells.
Figure 3: Facilitation of 3′ exonucleolytic degradation of bacterial mRNA decay intermediates by polyadenylation.
Figure 4: Pathways for 5′ end-dependent mRNA degradation in bacteria.
Figure 5: Pathways for the rapid degradation of bacterial and eukaryotic mRNAs that contain a premature termination codon.
Figure 6: Post-transcriptional downregulation by non-coding RNAs in eukaryotes and bacteria.

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References

  1. Tarun, S. Z., Jr & Sachs, A. B. Association of the yeast poly(A) tail binding protein with translation initiation factor eIF-4G. EMBO J. 15, 7168–7177 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Laursen, B. S., Sorensen, H. P., Mortensen, K. K. & Sperling-Petersen, H. U. Initiation of protein synthesis in bacteria. Microbiol. Mol. Biol. Rev. 69, 101–123 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Sonenberg, N. & Hinnebusch, A. G. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136, 731–745 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Jackson, R. J., Hellen, C. U. & Pestova, T. V. The mechanism of eukaryotic translation initiation and principles of its regulation. Nature Rev. Mol. Cell Biol. 11, 113–127 (2010).

    CAS  Google Scholar 

  5. Baird, S. D., Turcotte, M., Korneluk, R. G. & Holcik, M. Searching for IRES. RNA 12, 1755–1785 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Filbin, M. E. & Kieft, J. S. Toward a structural understanding of IRES RNA function. Curr. Opin. Struct. Biol. 19, 267–276 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Apirion, D. Degradation of RNA in Escherichia coli. A hypothesis. Mol. Gen. Genet. 122, 313–322 (1973).

    CAS  PubMed  Google Scholar 

  8. Belasco, J. G. & Higgins, C. F. Mechanisms of mRNA decay in bacteria: a perspective. Gene 72, 15–23 (1988).

    CAS  PubMed  Google Scholar 

  9. Apirion, D. Isolation, genetic mapping, and some characterization of a mutation in Escherichia coli that affects the processing of ribonucleic acids. Genetics 90, 659–671 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Ono, M. & Kuwano, M. A conditional lethal mutation in an Escherichia coli strain with a longer chemical lifetime of mRNA. J. Mol. Biol. 129, 343–357 (1979).

    CAS  PubMed  Google Scholar 

  11. Mudd, E. A., Krisch, H. M. & Higgins, C. F. RNase E, an endoribonuclease, has a general role in the chemical decay of E. coli mRNA: evidence that rne and ams are the same genetic locus. Mol. Microbiol. 4, 2127–2135 (1990).

    CAS  PubMed  Google Scholar 

  12. Babitzke, P. & Kushner, S. R. The Ams (altered mRNA stability) protein and ribonuclease E are encoded by the same structural gene of Escherichia coli. Proc. Natl Acad. Sci. USA 88, 1–5 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Melefors, Ö. & von Gabain, A. Genetic studies of cleavage-initiated mRNA decay and processing of ribosomal 9S RNA show that the Escherichia coli ams and rne loci are the same. Mol. Microbiol. 5, 857–864 (1991).

    CAS  PubMed  Google Scholar 

  14. Taraseviciene, L., Miczak, A. & Apirion, D. The gene specifying RNase E (rne) and a gene affecting mRNA stability (ams) are the same gene. Mol. Microbiol. 5, 851–855 (1991).

    CAS  PubMed  Google Scholar 

  15. McDowall, K. J., Lin-Chao, S. & Cohen, S. N. A+U content rather than a particular nucleotide order determines the specificity of RNase E cleavage. J. Biol. Chem. 269, 10790–10796 (1994).

    CAS  PubMed  Google Scholar 

  16. Emory, S. A., Bouvet, P. & Belasco, J. G. A 5'-terminal stem-loop structure can stabilize mRNA in Escherichia coli. Genes Dev. 6, 135–148 (1992).

    CAS  PubMed  Google Scholar 

  17. Bouvet, P. & Belasco, J. G. Control of RNase E-mediated RNA degradation by 5'-terminal base pairing in E. coli. Nature 360, 488–491 (1992).

    CAS  PubMed  Google Scholar 

  18. Hansen, M. J., Chen, L.-H., Fejzo, M. L. S. & Belasco, J. G. The ompA 5' untranslated region impedes a major pathway for mRNA degradation in Escherichia coli. Mol. Microbiol. 12, 707–716 (1994).

    CAS  PubMed  Google Scholar 

  19. Arnold, T. E., Yu, J. & Belasco, J. G. mRNA stabilization by the ompA 5' untranslated region: two protective elements hinder distinct pathways for mRNA degradation. RNA 4, 319–330 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Donovan, W. P. & Kushner, S. R. Polynucleotide phosphorylase and ribonuclease II are required for cell viability and mRNA turnover in Escherichia coli K-12. Proc. Natl Acad. Sci. USA 83, 120–124 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Ghosh, S. & Deutscher, M. P. Oligoribonuclease is an essential component of the mRNA decay pathway. Proc. Natl Acad. Sci. USA 96, 4372–4377 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Cheng, Z. F. & Deutscher, M. P. An important role for RNase R in mRNA decay. Mol. Cell 17, 313–318 (2005).

    CAS  PubMed  Google Scholar 

  23. Carpousis, A. J. The RNA degradosome of Escherichia coli: an mRNA-degrading machine assembled on RNase E. Annu. Rev. Microbiol. 61, 71–87 (2007).

    CAS  PubMed  Google Scholar 

  24. Shyu, A. B., Belasco, J. G. & Greenberg, M. E. Two distinct destabilizing elements in the c-fos message trigger deadenylation as a first step in rapid mRNA decay. Genes Dev. 5, 221–231 (1991).

    CAS  PubMed  Google Scholar 

  25. Decker, C. J. & Parker, R. A turnover pathway for both stable and unstable mRNAs in yeast: evidence for a requirement for deadenylation. Genes Dev. 7, 1632–1643 (1993).

    CAS  PubMed  Google Scholar 

  26. Muhlrad, D. & Parker, R. Mutations affecting stability and deadenylation of the yeast mfa2 transcript. Genes Dev. 6, 2100–2111 (1992).

    CAS  PubMed  Google Scholar 

  27. Muhlrad, D., Decker, C. J. & 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. 8, 855–866 (1994). This paper was the first to report that the deadenylation of eukaryotic mRNA triggers cap removal, thereby exposing the 5′ end to exonucleolytic attack by XRN1.

    CAS  PubMed  Google Scholar 

  28. 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 

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

    CAS  PubMed  Google Scholar 

  30. Jacobs Anderson, J. S. & 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).

    Google Scholar 

  31. von Gabain, A., Belasco, J. G., Schottel, J. L., Chang, A. C. Y. & Cohen, S. N. Decay of mRNA in Escherichia coli: investigation of the fate of specific segments of transcripts. Proc. Natl Acad. Sci. USA 80, 653–657 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Bricker, A. L. & Belasco, J. G. Importance of a 5′ stem-loop for longevity of papA mRNA in Escherichia coli. J. Bacteriol. 181, 3587–3590 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Baker, K. E. & Mackie, G. A. Ectopic RNase E sites promote bypass of 5′-end-dependent mRNA decay in Escherichia coli. Mol. Microbiol. 47, 75–88 (2003).

    CAS  PubMed  Google Scholar 

  34. Hambraeus, G., Karhumaa, K. & Rutberg, B. A 5′ stem-loop and ribosome binding but not translation are important for the stability of Bacillus subtilis aprE leader mRNA. Microbiology 148, 1795–1803 (2002).

    CAS  PubMed  Google Scholar 

  35. Sharp, J. S. & Bechhofer, D. H. Effect of 5′-proximal elements on decay of a model mRNA in Bacillus subtilis. Mol. Microbiol. 57, 484–495 (2005).

    CAS  PubMed  Google Scholar 

  36. Bechhofer, D. H. & Zen, K. H. Mechanism of erythromycin-induced ermC mRNA stability in Bacillus subtilis. J. Bacteriol. 171, 5803–5811 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Gottesman, M. E., Canellakis, Z. N. & Canellakis, E. S. Studies on the polymerization of adenylic acid by an enzyme of Escherichia coli. Biochim. Biophys. Acta 61, 34–42 (1962).

    CAS  PubMed  Google Scholar 

  38. August, J. T., Ortiz, P. J. & Hurwitz, J. Ribonucleic acid-dependent ribonucleotide incorporation. I. Purification and properties of the enzyme. J. Biol. Chem. 237, 3786–3793 (1962).

    CAS  PubMed  Google Scholar 

  39. Nakazato, H., Venkatesan, S. & Edmonds, M. Polyadenylic acid sequences in E. coli messenger RNA. Nature 256, 144–146 (1975).

    CAS  PubMed  Google Scholar 

  40. Srinivasan, P. R., Ramanarayanan, M. & Rabbani, E. Presence of polyriboadenylate sequences in pulse-labeled RNA of Escherichia coli. Proc. Natl Acad. Sci. USA 72, 2910–2914 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Cao, G. & Sarkar, N. Identification of the gene for an Escherichia coli poly(A) polymerase. Proc. Natl Acad. Sci. USA 89, 10380–10384 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Xu, F., Lin-Chao, S. & Cohen, S. N. The Escherichia coli pcnB gene promotes adenylylation of antisense RNAI of ColE1-type plasmids in vivo and degradation of RNAI decay intermediates. Proc. Natl Acad. Sci. USA 90, 6756–6760 (1993). This report was the first to reveal the function of bacterial poly(A) tails by showing that they expedite the degradation of RNA decay intermediates in E. coli.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Xu, F. & Cohen, S. N. RNA degradation in Escherichia coli regulated by 3′ adenylation and 5′ phosphorylation. Nature 374, 180–183 (1995).

    CAS  PubMed  Google Scholar 

  44. Hajnsdorf, E., Braun, F., Haugel-Nielsen, J. & Régnier, P. Polyadenylylation destabilizes the rpsO mRNA of Escherichia coli. Proc. Natl Acad. Sci. USA 92, 3973–3977 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Haugel-Nielsen, J., Hajnsdorf, E. & Régnier, P. The rpsO mRNA of Escherichia coli is polyadenylated at multiple sites resulting from endonucleolytic processing and exonucleolytic degradation. EMBO J. 15, 3144–3152 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Coburn, G. A., Miao, X., Briant, D. J. & Mackie, G. A. Reconstitution of a minimal RNA degradosome demonstrates functional coordination between a 3′ exonuclease and a DEAD-box RNA helicase. Genes Dev. 13, 2594–2603 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Marujo, P. E. et al. RNase II removes the oligo(A) tails that destabilize the rpsO mRNA of Escherichia coli. RNA 6, 1185–1193 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. O'Hara, E. B. et al. Polyadenylylation helps regulate mRNA decay in Escherichia coli. Proc. Natl Acad. Sci. USA 92, 1807–1811 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Schuster, G. & Stern, D. RNA polyadenylation and decay in mitochondria and chloroplasts. Prog. Mol. Biol. Transl. Sci. 85, 393–422 (2009).

    CAS  PubMed  Google Scholar 

  51. Meyer, S., Temme, C. & Wahle, E. Messenger RNA turnover in eukaryotes: pathways and enzymes. Crit. Rev. Biochem. Mol. Biol. 39, 197–216 (2004).

    CAS  PubMed  Google Scholar 

  52. LaCava, J. et al. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121, 713–724 (2005).

    CAS  PubMed  Google Scholar 

  53. Vanˇácˇová, S. et al. A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol. 3, e189 (2005). References 52 and 53 show that, as in bacteria, polyadenylation in yeast can stimulate 3′ exonucleolytic degradation of RNA in the nucleus.

    PubMed Central  Google Scholar 

  54. Rouge-maille, M. et al. Dissecting mechanisms of nuclear mRNA surveillance in THO/sub2 complex mutants. EMBO J. 26, 2317–2326 (2007).

    CAS  Google Scholar 

  55. San Paolo, S. et al. Distinct roles of non-canonical poly(A) polymerases in RNA metabolism. PLoS Genet. 5, e1000555 (2009).

    PubMed  Google Scholar 

  56. Nurmohamed, S., Vaidialingam, B., Callaghan, A. J. & Luisi, B. F. Crystal structure of Escherichia coli polynucleotide phosphorylase core bound to RNase E, RNA and manganese: implications for catalytic mechanism and RNA degradosome assembly. J. Mol. Biol. 389, 17–33 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Liu, Q., Greimann, J. C. & Lima, C. D. Reconstitution, activities, and structure of the eukaryotic RNA exosome. Cell 127, 1223–1237 (2006).

    CAS  PubMed  Google Scholar 

  58. Dziembowski, A., Lorentzen, E., Conti, E. & Seraphin, B. A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nature Struct. Mol. Biol. 14, 15–22 (2007). This paper shows that yeast exosomes derive their 3′ exonuclease activity from one or more associated RNases rather than from the exosome core.

    CAS  Google Scholar 

  59. Anderson, J. S. & 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Mackie, G. A. Ribonuclease E is a 5′-end-dependent endonuclease. Nature 395, 720–723 (1998). The original report showing that the rate of internal RNA cleavage by RNase E is strongly influenced by the phosphorylation state of the RNA 5′ end.

    CAS  PubMed  Google Scholar 

  62. Callaghan, A. J. et al. Structure of Escherichia coli RNase E catalytic domain and implications for RNA turnover. Nature 437, 1187–1191 (2005).

    CAS  PubMed  Google Scholar 

  63. Celesnik, H., Deana, A. & Belasco, J. G. Initiation of RNA decay in Escherichia coli by 5′ pyrophosphate removal. Mol. Cell 27, 79–90 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Deana, A., Celesnik, H. & Belasco, J. G. The bacterial enzyme RppH triggers messenger RNA degradation by 5′ pyrophosphate removal. Nature 451, 355–358 (2008). This paper identifies the RNA pyrophosphohydrolase that triggers 5′ end-dependent mRNA decay in E. coli , revealing it to be a homologue of the eukaryotic decapping enzyme DCP2.

    CAS  PubMed  Google Scholar 

  65. Stevens, A. & Poole, T. L. 5′-exonuclease-2 of Saccharomyces cerevisiae. Purification and features of ribonuclease activity with comparison to 5′-exonuclease-1. J. Biol. Chem. 270, 16063–16069 (1995).

    CAS  PubMed  Google Scholar 

  66. Shahbabian, K., Jamalli, A., Zig, L. & Putzer, H. RNase Y, a novel endoribonuclease, initiates riboswitch turnover in Bacillus subtilis. EMBO J. 28, 3523–3533 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Even, S. et al. Ribonucleases J1 and J2: two novel endoribonucleases in B. subtilis with functional homology to E. coli RNase E. Nucleic Acids Res. 33, 2141–2152 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Mathy, N. et al. 5′-to-3′ exoribonuclease activity in bacteria: role of RNase J1 in rRNA maturation and 5′ stability of mRNA. Cell 129, 681–692 (2007). This article shows that, like eukaryotes, some bacterial species contain a 5′ exoribonuclease.

    CAS  PubMed  Google Scholar 

  69. Commichau, F. M. et al. Novel activities of glycolytic enzymes in Bacillus subtilis: interactions with essential proteins involved in mRNA processing. Mol. Cell. Proteomics 8, 1350–1360 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Mäder, U., Zig, L., Kretschmer, J., Homuth, G. & Putzer, H. mRNA processing by RNases J1 and J2 affects Bacillus subtilis gene expression on a global scale. Mol. Microbiol. 70, 183–196 (2008).

    PubMed  Google Scholar 

  71. de la Sierra-Gallay, I. L., Zig, L., Jamalli, A. & Putzer, H. Structural insights into the dual activity of RNase J. Nature Struct. Mol. Biol. 15, 206–212 (2008).

    CAS  Google Scholar 

  72. Mullen, T. E. & Marzluff, W. F. Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5′ to 3′ and 3′ to 5′. Genes Dev. 22, 50–65 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Rissland, O. S. & Norbury, C. J. Decapping is preceded by 3′ uridylation in a novel pathway of bulk mRNA turnover. Nature Struct. Mol. Biol. 16, 616–623 (2009). This paper shows that Cid1-mediated uridylation at the 3′ end can trigger 5′ decapping and degradation of mRNA in Schizosaccharomyces pombe.

    CAS  Google Scholar 

  74. Hagan, J. P., Piskounova, E. & Gregory, R. I. Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells. Nature Struct. Mol. Biol. 16, 1021–1025 (2009).

    CAS  Google Scholar 

  75. Jones, M. R. et al. Zcchc11-dependent uridylation of microRNA directs cytokine expression. Nature Cell Biol. 11, 1157–1163 (2009).

    CAS  PubMed  Google Scholar 

  76. Tock, M. R., Walsh, A. P., Carroll, G. & McDowall, K. J. The CafA protein required for the 5′-maturation of 16 S rRNA is a 5′-end-dependent ribonuclease that has context-dependent broad sequence specificity. J. Biol. Chem. 275, 8726–8732 (2000).

    CAS  PubMed  Google Scholar 

  77. Nicholson, A. W. Function, mechanism and regulation of bacterial ribonucleases. FEMS Microbiol Rev. 23, 371–390 (1999).

    CAS  PubMed  Google Scholar 

  78. Binder, R. et al. Evidence that the pathway of transferrin receptor mRNA degradation involves an endonucleolytic cleavage within the 3′ UTR and does not involve poly(A) tail shortening. EMBO J. 13, 1969–1980 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Liu, J. et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305, 1437–1441 (2004).

    CAS  PubMed  Google Scholar 

  80. Meister, G. et al. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol. Cell 15, 185–197 (2004). References 79 and 80 identify AGO2 as the endonuclease that cleaves mRNAs targeted by fully complementary siRNAs during RNA interference in mammalian cells.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  82. Doma, M. K. & Parker, R. Endonucleolytic cleavage of eukaryotic mRNAs with stalls in translation elongation. Nature 440, 561–564 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Huntzinger, E., Kashima, I., Fauser, M., Sauliere, J. & Izaurralde, E. SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan. RNA 14, 2609–2617 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Eberle, A. B., Lykke-Andersen, S., Muhlemann, O. & Jensen, T. H. SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells. Nature Struct. Mol. Biol. 16, 49–55 (2009). References 83 and 84 identify SMG6 as the endonuclease that cleaves metazoan mRNAs containing a PTC.

    CAS  Google Scholar 

  85. Lorentzen, E., Basquin, J., Tomecki, R., Dziembowski, A. & Conti, E. Structure of the active subunit of the yeast exosome core, Rrp44: diverse modes of substrate recruitment in the RNase II nuclease family. Mol. Cell 29, 717–728 (2008).

    CAS  PubMed  Google Scholar 

  86. Schaeffer, D. et al. The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities. Nature Struct. Mol. Biol. 16, 56–62 (2009).

    CAS  Google Scholar 

  87. Lebreton, A., Tomecki, R., Dziembowski, A. & Seraphin, B. Endonucleolytic RNA cleavage by a eukaryotic exosome. Nature 456, 993–996 (2008).

    CAS  PubMed  Google Scholar 

  88. Matsushita, K. et al. Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay. Nature 458, 1185–1190 (2009).

    CAS  PubMed  Google Scholar 

  89. Skružný, M. et al. An endoribonuclease functionally linked to perinuclear mRNP quality control associates with the nuclear pore complexes. PLoS Biol. 7, e8 (2009).

    PubMed  Google Scholar 

  90. Liang, S. L., Quirk, D. & Zhou, A. RNase L: its biological roles and regulation. IUBMB Life 58, 508–514 (2006).

    CAS  PubMed  Google Scholar 

  91. Hollien, J. & Weissman, J. S. Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science 313, 104–107 (2006).

    CAS  PubMed  Google Scholar 

  92. Hollien, J. et al. Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J. Cell Biol. 186, 323–331 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Pastori, R. L., Moskaitis, J. E. & Schoenberg, D. R. Estrogen-induced ribonuclease activity in Xenopus liver. Biochemistry 30, 10490–10498 (1991).

    CAS  PubMed  Google Scholar 

  94. Nilsson, G., Belasco, J. G., Cohen, S. N. & von Gabain, A. Effect of premature termination of translation on mRNA stability depends on the site of ribosome release. Proc. Natl Acad. Sci. USA 84, 4890–4894 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Isken, O. & Maquat, L. E. Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function. Genes Dev. 21, 1833–1856 (2007).

    CAS  PubMed  Google Scholar 

  96. Zhang, J., Sun, X., Qian, Y. & Maquat, L. E. Intron function in the nonsense-mediated decay of β-globin mRNA: indications that pre-mRNA splicing in the nucleus can influence mRNA translation in the cytoplasm. RNA 4, 801–815 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Amrani, N. et al. A faux 3′-UTR promotes aberrant termination and triggers nonsense-mediated mRNA decay. Nature 432, 112–118 (2004).

    CAS  PubMed  Google Scholar 

  98. Bühler, M., Steiner, S., Mohn, F., Paillusson, A. & Mühlemann, O. EJC-independent degradation of nonsense immunoglobulin-μ mRNA depends on 3′ UTR length. Nature Struct. Mol. Biol. 13, 462–464 (2006).

    Google Scholar 

  99. Singh, G., Rebbapragada, I. & Lykke-Andersen, J. A competition between stimulators and antagonists of Upf complex recruitment governs human nonsense-mediated mRNA decay. PLoS Biol. 6, e111 (2008).

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  101. 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  PubMed  Google Scholar 

  102. Chen, C. Y. & Shyu, A. B. Rapid deadenylation triggered by a nonsense codon precedes decay of the RNA body in a mammalian cytoplasmic nonsense-mediated decay pathway. Mol. Cell. Biol. 23, 4805–4813 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Leeds, P., Peltz, S. W., Jacobson, A. & Culbertson, M. R. The product of the yeast Upf1 gene is required for rapid turnover of mRNAs containing a premature translational termination codon. Genes Dev. 5, 2303–2314 (1991).

    CAS  PubMed  Google Scholar 

  104. Leeds, P., Wood, J. M., Lee, B. S. & Culbertson, M. R. Gene products that promote mRNA turnover in Saccharomyces cerevisiae. Mol. Cell. Biol. 12, 2165–2177 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Cui, Y., Hagan, K. W., Zhang, S. & Peltz, S. W. Identification and characterization of genes that are required for the accelerated degradation of mRNAs containing a premature translational termination codon. Genes Dev. 9, 423–436 (1995).

    CAS  PubMed  Google Scholar 

  106. He, F., Brown, A. H. & Jacobson, A. Upf1p, Nmd2p, and Upf3p are interacting components of the yeast nonsense-mediated mRNA decay pathway. Mol. Cell. Biol. 17, 1580–1594 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. 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  Google Scholar 

  108. Richards, J., Mehta, P. & Karzai, A. W. RNase R degrades non-stop mRNAs selectively in an SmpB-tmRNA-dependent manner. Mol. Microbiol. 62, 1700–1712 (2006).

    CAS  PubMed  Google Scholar 

  109. Karzai, A. W., Roche, E. D. & Sauer, R. T. The SsrA-SmpB system for protein tagging, directed degradation and ribosome rescue. Nature Struct. Biol. 7, 449–455 (2000).

    CAS  PubMed  Google Scholar 

  110. Hayes, C. S. & Sauer, R. T. Cleavage of the A site mRNA codon during ribosome pausing provides a mechanism for translational quality control. Mol. Cell 12, 903–911 (2003).

    CAS  PubMed  Google Scholar 

  111. Sunohara, T., Jojima, K., Yamamoto, Y., Inada, T. & Aiba, H. Nascent-peptide-mediated ribosome stalling at a stop codon induces mRNA cleavage resulting in nonstop mRNA that is recognized by tmRNA. RNA 10, 378–386 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Sunohara, T., Jojima, K., Tagami, H., Inada, T. & Aiba, H. Ribosome stalling during translation elongation induces cleavage of mRNA being translated in Escherichia coli. J. Biol. Chem. 279, 15368–15375 (2004).

    CAS  PubMed  Google Scholar 

  113. Passos, D. O. et al. Analysis of Dom34 and its function in no-go decay. Mol. Biol. Cell 20, 3025–3032 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Mizuno, T., Chou, M. Y. & Inouye, M. A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA). Proc. Natl Acad. Sci. USA 81, 1966–1970 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Lee, R. C., Feinbaum, R. L. & Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843–854 (1993).

    CAS  PubMed  Google Scholar 

  116. Wightman, B., Ha, I. & Ruvkun, G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75, 855–862 (1993).

    CAS  PubMed  Google Scholar 

  117. Kim, V. N., Han, J. & Siomi, M. C. Biogenesis of small RNAs in animals. Nature Rev. Mol. Cell Biol. 10, 126–139 (2009).

    CAS  Google Scholar 

  118. Wu, L., Fan, J. & Belasco, J. G. MicroRNAs direct rapid deadenylation of mRNA. Proc. Natl Acad. Sci. USA 103, 4034–4039 (2006). This report shows that miRNAs accelerate the degradation of partially complementary mRNAs by expediting their deadenylation.

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Eulalio, A. et al. Deadenylation is a widespread effect of miRNA regulation. RNA 15, 21–32 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Zamore, P. D., Tuschl, T., Sharp, P. A. & Bartel, D. P. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101, 25–33 (2000). This paper was the first to determine the mechanism of RNA interference by showing that siRNAs direct endonucleolytic cleavage of the mRNAs to which they are fully complementary.

    CAS  PubMed  Google Scholar 

  121. Elbashir, S. M., Lendeckel, W. & Tuschl, T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 15, 188–200 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Wu, L., Fan, J. & Belasco, J. G. Importance of translation and nonnucleolytic Ago proteins for on-target RNA interference. Curr. Biol. 18, 1327–1332 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Chekulaeva, M., Filipowicz, W. & Parker, R. Multiple independent domains of dGW182 function in miRNA-mediated repression in Drosophila. RNA 15, 794–803 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Zipprich, J. T., Bhattacharyya, S., Mathys, H. & Filipowicz, W. Importance of the C-terminal domain of the human GW182 protein TNRC6C for translational repression. RNA 15, 781–793 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Lazzaretti, D., Tournier, I. & Izaurralde, E. The C-terminal domains of human TNRC6A, TNRC6B, and TNRC6C silence bound transcripts independently of Argonaute proteins. RNA 15, 1059–1066 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Waters, L. S. & Storz, G. Regulatory RNAs in bacteria. Cell 136, 615–628 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Bouvier, M., Sharma, C. M., Mika, F., Nierhaus, K. H. & Vogel, J. Small RNA binding to 5′ mRNA coding region inhibits translational initiation. Mol. Cell 32, 827–837 (2008).

    CAS  PubMed  Google Scholar 

  128. Darfeuille, F., Unoson, C., Vogel, J. & Wagner, E. G. An antisense RNA inhibits translation by competing with standby ribosomes. Mol. Cell 26, 381–392 (2007).

    CAS  PubMed  Google Scholar 

  129. Sharma, C. M., Darfeuille, F., Plantinga, T. H. & Vogel, J. A small RNA regulates multiple ABC transporter mRNAs by targeting C/A-rich elements inside and upstream of ribosome-binding sites. Genes Dev. 21, 2804–2817 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Majdalani, N., Cunning, C., Sledjeski, D., Elliott, T. & Gottesman, S. DsrA RNA regulates translation of RpoS message by an anti-antisense mechanism, independent of its action as an antisilencer of transcription. Proc. Natl Acad. Sci. USA 95, 12462–12467 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Majdalani, N., Hernandez, D. & Gottesman, S. Regulation and mode of action of the second small RNA activator of RpoS translation, RprA. Mol. Microbiol. 46, 813–826 (2002).

    CAS  PubMed  Google Scholar 

  132. Fröhlich, K. S. & Vogel, J. Activation of gene expression by small RNA. Curr. Opin. Microbiol. 12, 674–682 (2009).

    PubMed  Google Scholar 

  133. Massé, E., Escorcia, F. E. & Gottesman, S. Coupled degradation of a small regulatory RNA and its mRNA targets in Escherichia coli. Genes Dev. 17, 2374–2383 (2003).

    PubMed  PubMed Central  Google Scholar 

  134. Udekwu, K. I. et al. Hfq-dependent regulation of OmpA synthesis is mediated by an antisense RNA. Genes Dev. 19, 2355–2366 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Case, C. C., Simons, E. L. & Simons, R. W. The IS10 transposase mRNA is destabilized during antisense RNA control. EMBO J. 9, 1259–1266 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Huntzinger, E. et al. Staphylococcus aureus RNAIII and the endoribonuclease III coordinately regulate spa gene expression. EMBO J. 24, 824–835 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Pfeiffer, V., Papenfort, K., Lucchini, S., Hinton, J. C. & Vogel, J. Coding sequence targeting by MicC RNA reveals bacterial mRNA silencing downstream of translational initiation. Nature Struct. Mol. Biol. 16, 840–846 (2009).

    CAS  Google Scholar 

  138. Doench, J. G. & Sharp, P. A. Specificity of microRNA target selection in translational repression. Genes Dev. 18, 504–511 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297 (2004).

    CAS  PubMed  Google Scholar 

  140. Wang, Y., Sheng, G., Juranek, S., Tuschl, T. & Patel, D. J. Structure of the guide-strand-containing argonaute silencing complex. Nature 456, 209–213 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Hale, C. R. et al. RNA-guided RNA cleavage by a CRISPR RNA-Cas protein complex. Cell 139, 945–956 (2009). This article reports in vitro evidence that CRISPR RNAs, like eukaryotic siRNAs, can guide the endonucleolytic cleavage of fully complementary mRNAs in microorganisms that contain Cmr proteins.

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Haft, D. H., Selengut, J., Mongodin, E. F. & Nelson, K. E. A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes. PLoS Comput. Biol. 1, e60 (2005).

    PubMed  PubMed Central  Google Scholar 

  143. Chen, C. Y., Xu, N. & Shyu, A. B. mRNA decay mediated by two distinct AU-rich elements from c-fos and granulocyte-macrophage colony-stimulating factor transcripts: different deadenylation kinetics and uncoupling from translation. Mol. Cell. Biol. 15, 5777–5788 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Deana, A. & Belasco, J. G. Lost in translation: the influence of ribosomes on bacterial mRNA decay. Genes Dev. 19, 2526–2533 (2005).

    CAS  PubMed  Google Scholar 

  145. Folichon, M. et al. The poly(A) binding protein Hfq protects RNA from RNase E and exoribonucleolytic degradation. Nucleic Acids Res. 31, 7302–7310 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Selinger, D. W., Saxena, R. M., Cheung, K. J., Church, G. M. & Rosenow, C. Global RNA half-life analysis in Escherichia coli reveals positional patterns of transcript degradation. Genome Res. 13, 216–223 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  148. Mackie, G. A. Stabilization of circular rpsT mRNA demonstrates the 5′-end dependence of RNase E action in vivo. J. Biol. Chem. 275, 25069–25072 (2000).

    CAS  PubMed  Google Scholar 

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Acknowledgements

I am grateful to C. Condon and L. Bénard for their helpful comments. J.G.B. is supported by grants from the National Institutes of Health (GM35769 and GM79477).

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  1. Kimmel Center for Biology and Medicine at the Skirball Institute and Department of Microbiology, New York University School of Medicine, New York, 10016, USA

    Joel G. Belasco

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Glossary

Poly(A)-binding protein

A protein that binds 3′ poly(A) tails and eIF4F, thereby facilitating translation initiation and protecting mRNA from attack by exosomes and decapping enzymes.

Shine–Dalgarno element

A bacterial mRNA element that guides translation initiation at a downstream start codon by base pairing with the 3′ end of 16S rRNA.

Polycistronic mRNA

An mRNA that contains multiple translational units, each encoding a distinct protein.

Endonuclease

An enzyme that cleaves RNA or DNA at an internal position.

Exonuclease

An enzyme that degrades RNA or DNA by removing mononucleotides sequentially from the 5′ or 3′ end.

PNPase

A phosphorolytic bacterial 3′ exoribonuclease that can also act synthetically to add heteropolymeric tails to RNA.

Deadenylase

A 3′ exonuclease that is specific for degrading poly(A) tails.

Exosome

A protein complex that, in eukaryotes, comprises a nine-subunit core and other associated polypeptides. It uses its 3′ exonuclease activity, and to a lesser extent its endonuclease activity, to function in RNA processing and decay in the nucleus and cytoplasm.

TRAMP

A eukaryotic polyadenylation complex, comprising Trf, Air and Mtr4 proteins, that facilitates the 3′ exonucleolytic degradation of defective RNAs by nuclear exosomes.

RNase PH

A phosphorolytic 3′ exoribonuclease that is important for the maturation of the 3′ ends of bacterial tRNAs.

KH domain

A member of a family of RNA-binding domains that are homologous to the RNA-binding domains of heterogeneous nuclear ribonucleoprotein K (hnRNP K).

S1 domain

A member of a family of RNA-binding domains that are homologous to the RNA-binding domains of ribosomal protein S1.

Rrp6

A hydrolytic 3′ exoribonuclease that is associated with nuclear exosomes.

Rrp44

A bifunctional exosome-associated ribonuclease that contains both a hydrolytic 3′ exonuclease domain and an endonucleolytic PIN domain.

RNA pyrophosphohydrolase

An enzyme that can remove the γ- and β-phosphates from the 5′ end of a triphosphorylated transcript, converting it to a 5′ monophosphorylated RNA.

Nudix hydrolase

A member of a family of hydrolytic enzymes that share a characteristic sequence motif and catalyse the hydrolysis of substrates containing a nucleoside diphosphate as a constituent unit.

Argonaute

A member of a family of proteins that contain PAZ and PIWI domains and help to mediate RNA interference by binding siRNAs and miRNAs and delivering them to complementary mRNAs.

RNA interference

A eukaryotic regulatory process in which siRNAs or miRNAs repress gene expression by inhibiting the translation and accelerating the degradation of complementary mRNAs.

PIN domain

A member of a family of homologous protein domains that have endoribonuclease activity and are present in both eukaryotes and bacteria.

Premature termination codon

An in-frame UAA, UAG or UGA triplet that causes ribosomes to terminate translation upstream of the normal termination codon.

Exon junction

A site in a spliced eukaryotic mRNA where an intron was excised and the two flanking exons were joined.

tmRNA

A bifunctional aminoacylated RNA that has properties of both a tRNA and an mRNA and mediates the release of ribosomes from bacterial mRNAs that lack an in-frame translation termination codon.

Sm protein

A eukaryotic RNA-binding protein that assembles into a multimeric ring and binds RNA (for example, spliceosomal snRNA) in single-stranded regions that are typically U-rich.

Hfq

A bacterial RNA-binding protein, homologous to eukaryotic Sm and Sm-like proteins, that acts as a chaperone for many sRNAs and can also bind to mRNA and poly(A) tails.

CRISPR RNA

A bacterial or archaeal regulatory RNA, ∼30–60 nucleotides long, that is processed from the transcript of clustered regularly interspaced short palindromic repeats (CRISPRs) in chromosomal DNA.

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Belasco, J. All things must pass: contrasts and commonalities in eukaryotic and bacterial mRNA decay. Nat Rev Mol Cell Biol 11, 467–478 (2010). https://doi.org/10.1038/nrm2917

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