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Ribosome-Associated Quality Control in Bacteria

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Abstract

Translation of the genetic information into proteins, performed by the ribosome, is a key cellular process in all organisms. Translation usually proceeds smoothly, but, unfortunately, undesirable events can lead to stalling of translating ribosomes. To rescue these faulty arrested ribosomes, bacterial cells possess three well-characterized quality control systems, tmRNA, ArfA, and ArfB. Recently, an additional ribosome rescue mechanism has been discovered in Bacillus subtilis. In contrast to the “canonical” systems targeting the 70S bacterial ribosome, this latter mechanism operates by first splitting the ribosome into the small (30S) and large (50S) subunits to then clearing the resultant jammed large subunit from the incomplete nascent polypeptide. Here, I will discuss the recent microbiological, biochemical, and structural data regarding functioning of this novel rescue system.

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Abbreviations

CAT tail:

Carboxy-terminal Alanine and Threonine tail

RQC:

Ribosome-associated Quality Control

tmRNA:

transfer-messenger RNA

References

  1. Dai, X., Zhu, M., Warren, M., Balakrishnan, R., Patsalo, V., et al. (2016) Reduction of translating ribosomes enables Escherichia coli to maintain elongation rates during slow growth, Nat. Microbiol., 2, 16231.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Zhu, M., Dai, X., and Wang, Y.-P. (2016) Real time determination of bacterial in vivo ribosome translation elongation speed based on LacZα complementation system, Nucleic Acid Res., 44, e155.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Jha, S., and Komar, A. A. (2011) Birth, life and death of nascent polypeptide chains, Biotechnol. J., 6, 623-640.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Samatova, E., Daberger, J., Liutkute, M., and Rodnina, M. V. (2021) Translational control by ribosome pausing in bacteria: how a non-uniform pace of translation affects protein production and folding, Front. Microbiol., 11, 619430.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Doerfel, L. K., Wohlgemuth, I., Kothe, C., Peske, F., Urlaub, H., and Rodnina, M. V. (2013) EF-P is essential for rapid synthesis of proteins containing consecutive proline residues, Science, 339, 85-88.

    Article  CAS  PubMed  Google Scholar 

  6. Ude, S., Lassak, J., Starosta, A. L., Kraxenberger, T., Wilson, D. N., and Jung, K. (2013) Translation elongation factor EF-P alleviates ribosome stalling at polyproline stretches, Science, 339, 82-85.

    Article  CAS  PubMed  Google Scholar 

  7. Huter, P., Arenz, S., Bock, L. V., Graf, M., Frister, J. O., et al. (2017) Structural basis for polyproline-mediated ribosome stalling and rescue by the translation elongation factor EF-P, Mol. Cell, 68, 515-527.

    Article  CAS  PubMed  Google Scholar 

  8. Pech, M., Karim, Z., Yamamoto, H., Kitakawa, M., Qin, Y., and Nierhaus, K. H. (2011) Elongation factor 4 (EF4/LepA) accelerates protein synthesis at increased Mg2+ concentrations, Proc. Natl. Acad. Sci. USA, 108, 3199-3203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Betney, R., de Silva, E., Krishnan, J., and Stansfield, I. (2010) Autoregulatory systems controlling translation factor expression: thermostat-like control of translational accuracy, RNA, 16, 655-663.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Shalgi, R., Hurt, J. A., Krykbaeva, I., Taipale, M., Lindquist, S., and Burge, C. B. (2013) Widespread regulation of translation by elongation pausing in heat shock, Mol. Cell, 49, 439-452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Vazquez-Laslop, N., and Mankin, A. S. (2018) How macrolide antibiotics work, Trends Biochem. Sci., 43, 668-684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Muller, C., Crowe-McAuliffe, C., and Wilson, D. N. (2021) Ribosome rescue pathways in bacteria, Front. Microbiol., 12, 652980.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Buskirk, A. R., and Green, R. (2017) Ribosome pausing, arrest and rescue in bacteria and eukaryotes, Philos. Trans. R. Soc. Lond. B. Biol. Sci., 372, 20160183.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Keiler, K. C. (2015) Mechanisms of ribosome rescue in bacteria, Nat. Rev. Microbiol., 13, 285-297.

    Article  CAS  PubMed  Google Scholar 

  15. Keiler, K. C., Waller, P. R., and Sauer, R. T. (1996) Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA, Science, 271, 990-993.

    Article  CAS  PubMed  Google Scholar 

  16. Karzai, A. W., Susskind, M. M., and Sauer, R. T. (1999) SmpB, a unique RNA-binding protein essential for the peptide-tagging activity of SsrA (tmRNA), EMBO J., 18, 3793-3799.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Himeno, H., Nameki, N., Kurita, D., Muto, A., and Abo, T. (2015) Ribosome rescue systems in bacteria, Biochimie, 114, 102-112.

    Article  CAS  PubMed  Google Scholar 

  18. Chadani, Y., Ito, K., Kutsukake, K., and Abo, T. (2012) ArfA recruits release factor 2 to rescue stalled ribosomes by peptidyl-tRNA hydrolysis in Escherichia coli, Mol. Microbiol., 86, 37-50.

    Article  CAS  PubMed  Google Scholar 

  19. Shimizu, Y. (2012) ArfA recruits RF2 into stalled ribosomes, J. Mol. Biol., 423, 624-631.

    Article  CAS  PubMed  Google Scholar 

  20. Goralski, T. D. P., Kirimanjeswara, G. S., and Keiler, K. C. (2018) A new mechanism for ribosome rescue can recruit RF1 or RF2 to nonstop ribosomes, mBio, 9, e02436-18.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Handa, Y., Inaho, N., and Nameki, N. (2011) YaeJ is a novel ribosome-associated protein in Escherichia coli that can hydrolyze peptidyl-tRNA on stalled ribosomes, Nucleic Acids Res., 39, 1739-1748.

    Article  CAS  PubMed  Google Scholar 

  22. Gagnon, M. G., Seetharaman, S. V., Bulkley, D., and Steitz, T. A. (2012) Structural basis for the rescue of stalled ribosomes: structure of YaeJ bound to the ribosome, Science, 335, 1370-1372.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Shoemaker, C. J., and Green, R. (2012) Translation drives mRNA quality control, Nat. Struct. Mol. Biol., 19, 594-601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pisarev, A. V., Skabkin, M. A., Pisareva, V. P., Skabkina, O. V., Rakotondrafara, A. M., et al. (2010) The role of ABCE1 in eukaryotic post-termination ribosomal recycling, Mol. Cell, 37, 196-210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Shoemaker, C. J., Eyler, D. E., and Green, R. (2010) Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA drop-off to initiate no-go decay, Science, 330, 369-372.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Joazeiro, C. A. P. (2019) Mechanisms and functions of ribosome-associated protein quality control, Nat. Rev. Mol. Cell Biol., 20, 368-383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Shen, P. S., Park, J., Qin, Y., Li, X., Parsawar, K., et al. (2015) Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains, Science, 347, 75-78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Verma, R., Reichermeier, K. M., Burroughs, A. M., Oania, R. S., Reitsma, J. M., et al. (2018) Vms1/ANKZF1 peptidyl-tRNA hydrolases releases nascent chains from stalled ribosomes, Nature, 557, 446-451.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yip, M. C. J., Keszei, A. F. A., Feng, Q., Chu, V., McKenna, M. J., and Shao, S. (2019) Mechanism for recycling tRNAs on stalled ribosomes, Nat. Struct. Mol. Biol., 26, 343-349.

    Article  CAS  PubMed  Google Scholar 

  30. Yip, M. C. J., Savickas, S., Gygi, S. P., and Shao, S. (2020) ELAC1 repairs tRNA cleaved during ribosome-associated quality control, Cell Rep., 30, 2106-2114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chadani, Y., Ono, K., Kutsukake, K., and Abo, T. (2011) Escherichia coli YaeJ protein mediates a novel ribosome-rescue pathway distinct from SsrA- and ArfA-mediated pathways, Mol. Microbiol., 80, 772-785.

    Article  CAS  PubMed  Google Scholar 

  32. Keiler, K. C., and Feaga, H. A. (2014) Resolving nonstop translation complexes is a matter of life or death, J. Bacteriol., 196, 2123-2130.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Burroughs, A. M., and Aravind, L. (2014) Analysis of two domains with novel RNA-processing activities throws light on the complex evolution of ribosomal RNA biogenesis, Front. Genet., 5, 424.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Henderson, B., Nair, S., Pallas, J., and Williams, M. A. (2011) Fibronectin: a multidomain host adhesin targeted by bacterial fibronectin-binding proteins, FEMS Microbiol. Rev., 35, 147-200.

    Article  CAS  PubMed  Google Scholar 

  35. Lytvynenko, I., Paternoga, H., Thrun, A., Balke, A., Muller, T. A., et al. (2019) Alanine tails signal proteolysis in bacterial ribosome-associated quality control, Cell, 178, 76-90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Filbeck, S., Cerullo, F., Paternoga, H., Tsaprailis, G., Joazeiro, C. A. P., and Pfeffer, S. (2021) Mimicry of canonical translation elongation underlies alanine tail synthesis in RQC, Mol. Cell, 81, 104-114.

    Article  CAS  PubMed  Google Scholar 

  37. Crowe-McAuliffe, C., Takada, H., Murina, V., Polte, C., Kasvandik, S., et al. (2021) Structural basis for bacterial ribosome-associated quality control by RqcH and RqcP, Mol. Cell, 81, 115-126.

    Article  CAS  PubMed  Google Scholar 

  38. Chadani, Y., Niwa, T., Izumi, T., Sugata, N., Nagao, A., et al. (2017) Intrinsic ribosome destabilization underlies translation and provides an organism with a strategy of environmental sensing, Mol. Cell, 68, 528-539.

    Article  CAS  PubMed  Google Scholar 

  39. Chadani, Y., Sugata, N., Niwa, T., Ito, Y., Iwasaki, S., and Taguchi, H. (2021) Nascent polypeptide within the exit tunnel ensures continuous translation elongation by stabilizing the translating ribosome, bioRxiv, https://doi.org/10.1101/2021.02.02.429294.

    Article  Google Scholar 

  40. Peske, F., Rodnina, M. V., and Wintermeyer, W. (2005) Sequence of steps in ribosome recycling as defined by kinetic analysis, Mol. Cell, 18, 403-412.

    Article  CAS  PubMed  Google Scholar 

  41. Zhang, Y., Mandava, C. S., Cao, W., Li, X., Zhang, D., et al. (2015) HflX is a ribosome-splitting factor rescuing stalled ribosomes under stress conditions, Nat. Struct. Mol. Biol., 22, 906-913.

    Article  CAS  PubMed  Google Scholar 

  42. Tomar, S. K., Kumar, P., and Prakash, B. (2011) Deciphering the catalytic machinery in a universally conserved ribosome binding ATPase YchF, Biochem. Biophys. Res. Commun., 408, 459-464.

    Article  CAS  PubMed  Google Scholar 

  43. Feng, B., Mandava, C. S., Guo, Q., Wang, J., Cao, W., et al. (2014) Structural and functional insights into the mode of action of a universally conserved Obg GTPase, PLos Biol., 12, e1001866.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Korber, P., Stahl, J. M., Nierhaus, K. H., and Bardwell, J. C. (2000) Hsp15: a ribosome-associated heat shock protein, EMBO J., 19, 741-748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jiang, L., Schaffitzel, C., Bingel-Erlenmeyer, R., Ban, N., Korber, P., et al. (2009) Recycling of aborted ribosomal 50S subunit-nascent chain-tRNA complexes by the heat shock protein Hsp15, J. Mol. Biol., 386, 1357-1367.

    Article  CAS  PubMed  Google Scholar 

  46. Starosta, A. L., Lassak, J., Jung, K., and Wilson, D. N. (2014) The bacterial translation stress response, FEMS Microbiol. Rev., 38, 1172-1201.

    Article  CAS  PubMed  Google Scholar 

  47. Das, G., and Varshney, U. (2006) Peptidyl-tRNA hydrolase and its critical role in protein biosynthesis, Microbiology, 152, 2191-2195.

    Article  CAS  PubMed  Google Scholar 

  48. Sharma, S., Kaushik, S., Sinha, M., Kushwaha, G. S., Singh, A., et al. (2014) Structural and functional insights into peptidyl-tRNA hydrolase, Biochim. Biophys. Acta, 1844, 1279-1288.

    Article  CAS  PubMed  Google Scholar 

  49. Burroughs, A. M., and Aravind, L. (2019) The origin and evolution of release factors: implications for translation termination, ribosome rescue, and quality control pathways, Int. J. Mol. Sci., 20, 1981.

    Article  CAS  PubMed Central  Google Scholar 

  50. Lewis, K. (2020) The science of antibiotic discovery, Cell, 181, 29-45.

    Article  CAS  PubMed  Google Scholar 

  51. Holmes, A. R., McNab, R., Millsap, K. W., Rohde, M., Hammerschmidt, S., et al. (2001) The pavA gene of Streptococcus pneumoniae encodes a fibronectin-binding protein that is essential for virulence, Mol. Microbiol., 41, 1395-1408.

    Article  CAS  PubMed  Google Scholar 

  52. Pracht, D., Elm, C., Gerber, J., Bergmann, S., Rohde, M., et al. (2005) PavA of Streptococcus pneumoniae modulates adherence, invasion, and meningeal inflammation, Infect. Immun., 73, 2680-2689.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Singh, K. V., La Rossa, S. L., Somarajan, S. R., Roh, J. H., and Murray, B. E. (2015) The fibronectin-binding protein EfbA contributes to pathogenesis and protects against infective endocarditis caused by Enterococcus faecalis, Infect. Immun., 83, 4487-4494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Dramsi, S., Bourdichon, F., Cabanes, D., Lecuit, M., Fsihi, H., and Cossart, P. (2004) FbpA, a novel multifunctional Listeria monocytogenes virulence factor, Mol. Microbiol., 53, 639-649.

    Article  CAS  PubMed  Google Scholar 

  55. Ramadoss, N. S., Alumasa, J. N., Cheng, L., Wang, Y., Li, S., et al. (2013) Small molecule inhibitors of trans-translation have broad-spectrum antibiotic activity, Proc. Natl. Acad. Sci. USA, 110, 10282-10287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Aron, Z. D., Mehrani, A., Hoffer, E. D., Connolly, K. L., Srinivas, P., et al. (2021) trans-Translation inhibitors bind to a novel site on the ribosome and clear Neisseria gonorrhoeae in vivo, Nat. Commun., 12, 1799.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

I want to express my deepest gratitude to my teacher Dr. Alexander Spirin and members of the Institute of Protein Research in Pushchino, where I gained priceless experience in the fields of protein biosynthesis and ribosomology. I am grateful to Alexander Richardson, Dr. Yury Polikanov, Dr. Nora Vázquez-Laslop, and Dr. Alexander Mankin for critical reading and fruitful discussion of the review.

Funding

This work was supported by the NIH grant R21-AI137584.

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  1. Center for Biomolecular Sciences, Department of Pharmaceutical Sciences, University of Illinois at Chicago, 60607, Chicago, Illinois, USA

    Maxim S. Svetlov

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Correspondence to Maxim S. Svetlov.

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The author declares no conflicts of interest in financial or any other sphere. This article does not contain any studies involving human participants or animals performed by the author.

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Svetlov, M.S. Ribosome-Associated Quality Control in Bacteria. Biochemistry Moscow 86, 942–951 (2021). https://doi.org/10.1134/S0006297921080058

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