Mechanisms of ribosome rescue in bacteria

Nature Reviews Microbiology

Volumn 13, Issue 5, 2015, Pages 285-297

  Keiler, Kenneth C ^a  

^a PENNSYLVANIA STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ELONGATION FACTOR; MESSENGER RNA;

AMINO ACID SEQUENCE; BACTERIUM; NONHUMAN; PRIORITY JOURNAL; REVIEW; RIBOSOME; RNA BINDING; RNA TRANSLATION; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; PHYSIOLOGY; PROTEIN SYNTHESIS;

BACTERIA; GENE EXPRESSION REGULATION, BACTERIAL; PROTEIN BIOSYNTHESIS; RIBOSOMES;

EID: 84928433497     PISSN: 17401526     EISSN: 17401534     Source Type: Journal    
DOI: 10.1038/nrmicro3438     Document Type: Review

References (132)

1. Russell, J. B. & Cook, G. M. Energetics of bacterial growth: balance of anabolic and catabolic reactions. Microbiol. Rev. 59, 48-62 (1995).
2. Li, G.W., Burkhardt, D., Gross, C. & Weissman, J. S. Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources. Cell 157, 624-635 (2014).
3. Schmeing, T. M. & Ramakrishnan, V. What recent ribosome structures have revealed about the mechanism of translation. Nature 461, 1234-1242 (2009).
4. Siwiak, M. & Zielenkiewicz, P. Transimulation - protein biosynthesis web service. PLoS ONE 8, e73943 (2013).
5. Keiler, K. C. & Feaga, H. A. Resolving nonstop translation complexes is a matter of life or death. J. Bacteriol. 196, 2123-2130 (2014).
6. Ivanova, N., Pavlov, M. Y. & Ehrenberg, M. tmRNA-induced release of messenger RNA from stalled ribosomes. J. Mol. Biol. 350, 897-905 (2005).
7. Gonzalez de Valdivia, E. I. & Isaksson, L. A. Abortive translation caused by peptidyl-tRNA drop-off at NGG codons in the early coding region of mRNA. FEBS J. 272, 5306-5316 (2005).
8. Cruz-Vera, L. R., Magos-Castro, M. A., Zamora-Romo, E. & Guarneros, G. Ribosome stalling and peptidyl-tRNA drop-off during translational delay at AGA codons. Nucleic Acids Res. 32, 4462-4468 (2004).
9. Moore, S. D. & Sauer, R. T. Ribosome rescue: tmRNA tagging activity and capacity in Escherichia coli. Mol. Microbiol. 58, 456-466 (2005).
10. Ramadoss, N. S. et al. Small molecule inhibitors of trans-translation have broad-spectrum antibiotic activity. Proc. Natl Acad. Sci. USA 110, 10282-10287 (2013). This paper describes the identification of trans-translation inhibitors and demonstrates that they have antibacterial activity.
11. Ramadoss, N. S., Zhou, X. & Keiler, K. C. tmRNA is essential in Shigella flexneri. PLoS ONE 8, e57537 (2013).
12. Chadani, Y. et al. Ribosome rescue by Escherichia coli ArfA (YhdL) in the absence of trans-translation system. Mol. Microbiol. 78, 796-808 (2010). This paper describes the discovery of ArfA and demonstrates that at least one mechanism for ribosome rescue is required in E. coli.
13. Keiler, K. C., Waller, P. R. & Sauer, R. T. Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA. Science 271, 990-993 (1996). This paper describes the discovery of trans-translation.
14. Karzai, A. W., Susskind, M. M. & Sauer, R. T. SmpB, a unique RNA-binding protein essential for the peptide-tagging activity of SsrA (tmRNA). EMBO J. 18, 3793-3799 (1999). This study shows that SmpB binds to tmRNA and is required for trans-translation.
15. Bessho, Y. et al. Structural basis for functional mimicry of long-variable-arm tRNA by transfer-messenger RNA. Proc. Natl Acad. Sci. USA 104, 8293-8298 (2007).
16. Komine, Y., Kitabatake, M., Yokogawa, T., Nishikawa, K. & Inokuchi, H. A tRNA-like structure is present in 10Sa RNA, a small stable RNA from Escherichia coli. Proc. Natl Acad. Sci. USA 91, 9223-9227 (1994).
17. Yamamoto, Y., Sunohara, T., Jojima, K., Inada, T. & Aiba, H. SsrA-mediated trans-translation plays a role in mRNA quality control by facilitating degradation of truncated mRNAs. RNA 9, 408-418 (2003).
18. Hudson, C. M., Lau, B. Y. & Williams, K. P. Ends of the line for tmRNA-SmpB. Front. Microbiol. 5, 421 (2014).
19. Shimizu, Y. ArfA recruits RF2 into stalled ribosomes. J. Mol. Biol. 423, 624-631 (2012).
20. Chadani, Y., Ono, K., Kutsukake, K. & Abo, T. Escherichia coli YaeJ protein mediates a novel ribosome-rescue pathway distinct from SsrA- and ArfA-mediated pathways. Mol. Microbiol. 80, 772-785 (2011). This paper describes the discovery of ArfB.
21. Kurita, D., Chadani, Y., Muto, A., Abo, T. & Himeno, H. ArfA recognizes the lack of mRNA in the mRNA channel after RF2 binding for ribosome rescue. Nucleic Acids Res. 42, 13339-13352 (2014).
22. Ivanova, N., Pavlov, M. Y., Felden, B. & Ehrenberg, M. Ribosome rescue by tmRNA requires truncated mRNAs. J. Mol. Biol. 338, 33-41 (2004). This paper presents in vitro assays that show that trans-translation is much faster when the mRNA does not extend past the leading edge of the ribosome.
23. Moore, S. D. & Sauer, R. T. The tmRNA system for translational surveillance and ribosome rescue. Annu. Rev. Biochem. 76, 101-124 (2007).
24. Li, G.-W., Oh, E. & Weissman, J. S. The anti-Shine-Dalgarno sequence drives translational pausing and codon choice in bacteria. Nature 484, 538-541 (2012).
25. Schrader, J. M. et al. The coding and noncoding architecture of the Caulobacter crescentus genome. PLoS Genet. 10, e1004463 (2014).
26. Shoji, S., Janssen, B. D., Hayes, C. S. & Fredrick, K. Translation factor LepA contributes to tellurite resistance in Escherichia coli but plays no apparent role in the fidelity of protein synthesis. Biochimie 92, 157-163 (2010).
27. Elgamal, S. et al. EF-P dependent pauses integrate proximal and distal signals during translation. PLoS Genet. 10, e1004553 (2014). This study uses ribosome profiling to identify sites of translation stalling that can be relieved by EF-P.
28. Cruz-Vera, L. R., Sachs, M. S., Squires, C. L. & Yanofsky, C. Nascent polypeptide sequences that influence ribosome function. Curr. Opin. Microbiol. 14, 160-166 (2011).
29. Doerfel, L. K. et al. EF-P is essential for rapid synthesis of proteins containing consecutive proline residues. Science 339, 85-88 (2013).
30. Ude, S. et al. Translation elongation factor EF-P alleviates ribosome stalling at polyproline stretches. Science 339, 82-85 (2013). References 29 and 30 demonstrate that ribosomes stall at polyproline sequences in the absence of EF-P.
31. Li, X., Hirano, R., Tagami, H. & Aiba, H. Protein tagging at rare codons is caused by tmRNA action at the 3' end of nonstop mRNA generated in response to ribosome stalling. RNA 12, 248-255 (2006).
32. Li, X., Yokota, T., Ito, K., Nakamura, Y. & Aiba, H. Reduced action of polypeptide release factors induces mRNA cleavage and tmRNA tagging at stop codons in Escherichia coli. Mol. Microbiol. 63, 116-126 (2007).
33. Janssen, B. D., Garza-Sánchez, F. & Hayes, C. S. A-site mRNA cleavage is not required for tmRNA-mediated ssrA-peptide tagging. PLoS ONE 8, e81319 (2013).
34. Garza-Sánchez, F. et al. Amino acid starvation and colicin D treatment induce A-site mRNA cleavage in Escherichia coli. J. Mol. Biol. 378, 505-519 (2008).
35. 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).
36. 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).
37. 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).
38. Garza-Sánchez, F., Shoji, S., Fredrick, K. & Hayes, C. S. RNase II is important for A-site mRNA cleavage during ribosome pausing. Mol. Microbiol. 73, 882-897 (2009).
39. Pedersen, K. et al. The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site. Cell 112, 131-140 (2003).
40. Christensen, S. K., Pedersen, K., Hansen, F. G. & Gerdes, K. Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA. J. Mol. Biol. 332, 809-819 (2003).
41. Christensen, S. K. & Gerdes, K. RelE toxins from bacteria and Archaea cleave mRNAs on translating ribosomes, which are rescued by tmRNA. Mol. Microbiol. 48, 1389-1400 (2003). References 40 and 41show that toxin-mediated mRNA cleavage targets ribosomes to rescue pathways.
42. Doma, M. K. & Parker, R. RNA quality control in eukaryotes. Cell 131, 660-668 (2007).
43. Laursen, B. S., Sørensen, H. P., Mortensen, K. K. & Sperling-Petersen, H. U. Initiation of protein synthesis in bacteria. Microbiol. Mol. Biol. Rev. 69, 101-123 (2005).
44. Ito, K. et al. Nascentome analysis uncovers futile protein synthesis in Escherichia coli. PLoS ONE 6, e28413 (2011).
45. Atkins, J. F. & Gesteland, R. F. A case for trans-translation. Nature 379, 769-771 (1996).
46. Gutmann, S. et al. Crystal structure of the transfer-RNA domain of transfer-messenger RNA in complex with SmpB. Nature 424, 699-703 (2003).
47. Ushida, C. et al. tRNA-like structures in 10Sa RNAs of Mycoplasma capricolum and Bacillus subtilis. Nucleic Acids Res. 22, 3392-3396 (1994).
48. Barends, S., Wower, J. & Kraal, B. Kinetic parameters for tmRNA binding to alanyl-tRNA synthetase and elongation factor Tu from Escherichia coli. Biochemistry 39, 2652-2658 (2000).
49. Rudinger-Thirion, J., Giegé, R. & Felden, B. Aminoacylated tmRNA from Escherichia coli interacts with prokaryotic elongation factor Tu. RNA 5, 989-992 (1999).
50. Felden, B., Himeno, H., Muto, A., Atkins, J. F. & Gesteland, R. F. Structural organization of Escherichia coli tmRNA. Biochimie 78, 979-983 (1996).
51. Tu, G. F., Reid, G. E., Zhang, J. G., Moritz, R. L. & Simpson, R. J. C-terminal extension of truncated recombinant proteins in Escherichia coli with a 10Sa RNA decapeptide. J. Biol. Chem. 270, 9322-9326 (1995).
52. Williams, K. P. & Bartel, D. P. Phylogenetic analysis of tmRNA secondary structure. RNA 2, 1306-1310 (1996).
53. Williams, K. P., Martindale, K. A. & Bartel, D. P. Resuming translation on tmRNA: a unique mode of determining a reading frame. EMBO J. 18, 5423-5433 (1999).
54. Keiler, K. C., Shapiro, L. & Williams, K. P. tmRNAs that encode proteolysis-inducing tags are found in all known bacterial genomes: a two-piece tmRNA functions in Caulobacter. Proc. Natl Acad. Sci. USA 97, 7778-7783 (2000).
55. Keiler, K. C. & Shapiro, L. tmRNA is required for correct timing of DNA replication in Caulobacter crescentus. J. Bacteriol. 185, 573-580 (2003).
56. Wiegert, T. & Schumann, W. SsrA-mediated tagging in Bacillus subtilis. J. Bacteriol. 183, 3885-3889 (2001).
57. Valle, M. et al. Visualizing tmRNA entry into a stalled ribosome. Science 300, 127-130 (2003).
58. Neubauer, C., Gillet, R., Kelley, A. C. & Ramakrishnan, V. Decoding in the absence of a codon by tmRNA and SmpB in the ribosome. Science 335, 1366-1369 (2012). This study shows how the tmRNA-SmpB complex recognizes the absence of an mRNA sequence beyond the decoding centre in a non-stop ribosome.
59. Kurita, D., Muto, A. & Himeno, H. Role of the C-terminal tail of SmpB in the early stage of trans-translation. RNA 16, 980-990 (2010).
60. Sundermeier, T. R., Dulebohn, D. P., Cho, H. J. & Karzai, A. W. A previously uncharacterized role for small protein B (SmpB) in transfer messenger RNA-mediated trans-translation. Proc. Natl Acad. Sci. USA 102, 2316-2321 (2005).
61. Miller, M. R. & Buskirk, A. R. An unusual mechanism for EF-Tu activation during tmRNA-mediated ribosome rescue. RNA 20, 228-235 (2014).
62. Kurita, D., Miller, M. R., Muto, A., Buskirk, A. R. & Himeno, H. Rejection of tmRNA·SmpB after GTP hydrolysis by EF-Tu on ribosomes stalled on intact mRNA. RNA 20, 1706-1714 (2014).
63. Weis, F. et al. tmRNA-SmpB: a journey to the centre of the bacterial ribosome. EMBO J. 29, 3810-3818 (2010).
64. Ramrath, D. J. et al. The complex of tmRNA-SmpB and EF-G on translocating ribosomes. Nature 485, 526-529 (2012).
65. Fu, J. et al. Visualizing the transfer-messenger RNA as the ribosome resumes translation. EMBO J. 29, 3819-3825 (2010).
66. Konno, T., Kurita, D., Takada, K., Muto, A. & Himeno, H. A functional interaction of SmpB with tmRNA for determination of the resuming point of trans-translation. RNA 13, 1723-1731 (2007).
67. Lee, S., Ishii, M., Tadaki, T., Muto, A. & Himeno, H. Determinants on tmRNA for initiating efficient and precise trans-translation: some mutations upstream of the tag-encoding sequence of Escherichia coli tmRNA shift the initiation point of trans-translation in vitro. RNA 7, 999-1012 (2001).
68. Choy, J. S., Aung, L. L. & Karzai, A. W. Lon protease degrades transfer-messenger RNA-tagged proteins. J. Bacteriol. 189, 6564-6571 (2007).
69. Gottesman, S., Roche, E., Zhou, Y. & Sauer, R. T. The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system. Genes Dev. 12, 1338-1347 (1998).
70. Herman, C., Thévenet, D., Bouloc, P., Walker, G. C. & D'Ari, R. Degradation of carboxy-terminal-tagged cytoplasmic proteins by the Escherichia coli protease HflB (FtsH). Genes Dev. 12, 1348-1355 (1998).
71. Flynn, J. M. et al. Overlapping recognition determinants within the ssrA degradation tag allow modulation of proteolysis. Proc. Natl Acad. Sci. USA 98, 10584-10589 (2001).
72. 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).
73. Mehta, P., Richards, J. & Karzai, A. W. tmRNA determinants required for facilitating nonstop mRNA decay. RNA 12, 2187-2198 (2006).
74. Venkataraman, K., Zafar, H. & Karzai, A. W. Distinct tmRNA sequence elements facilitate RNase R engagement on rescued ribosomes for selective nonstop mRNA decay. Nucleic Acids Res. 42, 11192-11202 (2015). This work demonstrates that sequences in tmRNA are required for RNase R-mediated degradation of non-stop mRNAs.
75. Ge, Z., Mehta, P., Richards, J. & Karzai, A. W. Non-stop mRNA decay initiates at the ribosome. Mol. Microbiol. 78, 1159-1170 (2010).
76. Venkataraman, K., Guja, K. E., Garcia-Diaz, M. & Karzai, A. W. Non-stop mRNA decay: a special attribute of trans-translation mediated ribosome rescue. Front. Microbiol. 5, 93 (2014).
77. Chadani, Y., Ito, K., Kutsukake, K. & Abo, T. ArfA recruits release factor 2 to rescue stalled ribosomes by peptidyl-tRNA hydrolysis in Escherichia coli. Mol. Microbiol. 86, 37-50 (2012).
78. Garza-Sánchez, F., Schaub, R. E., Janssen, B. D. & Hayes, C. S. tmRNA regulates synthesis of the ArfA ribosome rescue factor. Mol. Microbiol. 80, 1204-1219 (2011).
79. Chadani, Y. et al. Trans-translation-mediated tight regulation of the expression of the alternative ribosome-rescue factor ArfA in Escherichia coli. Genes Genet. Syst. 86, 151-163 (2011).
80. Schaub, R. E., Poole, S. J., Garza-Sánchez, F., Benbow, S. & Hayes, C. S. Proteobacterial ArfA peptides are synthesized from non-stop messenger RNAs. J. Biol. Chem. 287, 29765-29775 (2012).
81. Feaga, H. A., Viollier, P. H. & Keiler, K. C. Release of nonstop ribosomes is essential. mBio 5, e01916 (2014).
82. Handa, Y., Inaho, N. & Nameki, N. YaeJ is a novel ribosome-associated protein in Escherichia coli that can hydrolyze peptidyl-tRNA on stalled ribosomes. Nucleic Acids Res. 39, 1739-1748 (2011).
83. Gagnon, M. G. et al. Structural basis for the rescue of stalled ribosomes: structure of YaeJ bound to the ribosome. Science 335, 1370-1372 (2012).
84. Kogure, H. et al. Identification of residues required for stalled-ribosome rescue in the codon-independent release factor YaeJ. Nucleic Acids Res. 42, 3152-3163 (2014).
85. Huang, C., Wolfgang, M. C., Withey, J., Koomey, M. & Friedman, D. I. Charged tmRNA but not tmRNA-mediated proteolysis is essential for Neisseria gonorrhoeae viability. EMBO J. 19, 1098-1107 (2000).
86. Personne, Y. & Parish, T. Mycobacterium tuberculosis possesses an unusual tmRNA rescue system. Tuberculosis (Edinb.) 94, 34-42 (2014).
87. Thibonnier, M., Thiberge, J.-M. & De Reuse, H. Trans-translation in Helicobacter pylori: essentiality of ribosome rescue and requirement of protein tagging for stress resistance and competence. PLoS ONE 3, e3810 (2008).
88. Fey, P. D. et al. A genetic resource for rapid and comprehensive phenotype screening of nonessential Staphylococcus aureus genes. mBio 4, e00537-12 (2013).
89. Chaudhuri, R. R. et al. Comprehensive identification of essential Staphylococcus aureus genes using transposon-mediated differential hybridisation (TMDH). BMC Genomics 10, 291 (2009).
90. Glass, J. I. et al. Essential genes of a minimal bacterium. Proc. Natl Acad. Sci. USA 103, 425-430 (2006).
91. Keiler, K. C. Biology of trans-translation. Annu. Rev. Microbiol. 62, 133-151 (2008).
92. Abo, T., Ueda, K., Sunohara, T., Ogawa, K. & Aiba, H. SsrA-mediated protein tagging in the presence of miscoding drugs and its physiological role in Escherichia coli. Genes Cells 7, 629-638 (2002).
93. Li, J., Ji, L., Shi, W., Xie, J. & Zhang, Y. Trans-translation mediates tolerance to multiple antibiotics and stresses in Escherichia coli. J. Antimicrob. Chemother. 68, 2477-2481 (2013).
94. Muto, A. et al. Requirement of transfer-messenger RNA for the growth of Bacillus subtilis under stresses. Genes Cells 5, 627-635 (2000).
95. Shin, J.-H. & Price, C. W. The SsrA-SmpB ribosome rescue system is important for growth of Bacillus subtilis at low and high temperatures. J. Bacteriol. 189, 3729-3737 (2007).
96. Julio, S. M., Heithoff, D. M. & Mahan, M. J. ssrA (tmRNA) plays a role in Salmonella enterica serovar Typhimurium pathogenesis. J. Bacteriol. 182, 1558-1563 (2000).
97. Svetlanov, A., Puri, N., Mena, P., Koller, A. & Karzai, A. W. Francisella tularensis tmRNA system mutants are vulnerable to stress, avirulent in mice, and provide effective immune protection. Mol. Microbiol. 85, 122-141 (2012).
98. Okan, N. A., Mena, P., Benach, J. L., Bliska, J. B. & Karzai, A. W. The smpB-ssrA mutant of Yersinia pestis functions as a live attenuated vaccine to protect mice against pulmonary plague infection. Infect. Immun. 78, 1284-1293 (2010).
99. Nudler, E., Avetissova, E., Markovtsov, V. & Goldfarb, A. Transcription processivity: protein-DNA interactions holding together the elongation complex. Science 273, 211-217 (1996).
100. Bandyra, K. J. & Luisi, B. F. Licensing and due process in the turnover of bacterial RNA. RNA Biol. 10, 627-635 (2013).
101. Zhang, Y. et al. MazF cleaves cellular mRNAs specifically at ACA to block protein synthesis in Escherichia coli. Mol. Cell 12, 913-923 (2003).
102. Maisonneuve, E., Shakespeare, L. J., Jørgensen, M. G. & Gerdes, K. Bacterial persistence by RNA endonucleases. Proc. Natl Acad. Sci. USA 108, 13206-13211 (2011).
103. Ueda, K. et al. Bacterial SsrA system plays a role in coping with unwanted translational readthrough caused by suppressor tRNAs. Genes Cells 7, 509-519 (2002).
104. Hayes, C. S., Bose, B. & Sauer, R. T. Proline residues at the C terminus of nascent chains induce SsrA tagging during translation termination. J. Biol. Chem. 277, 33825-33832 (2002).
105. Hayes, C. S., Bose, B. & Sauer, R. T. Stop codons preceded by rare arginine codons are efficient determinants of SsrA tagging in Escherichia coli. Proc. Natl Acad. Sci. USA 99, 3440-3445 (2002).
106. Caliskan, N., Katunin, V. I., Belardinelli, R., Peske, F. & Rodnina, M. V. Programmed -1 frameshifting by kinetic partitioning during impeded translocation. Cell 157, 1619-1631 (2014).
107. Woolstenhulme, C. J. et al. Nascent peptides that block protein synthesis in bacteria. Proc. Natl Acad. Sci. USA 110, E878-E887 (2013).
108. Roche, E. D. & Sauer, R. T. SsrA-mediated peptide tagging caused by rare codons and tRNA scarcity. EMBO J. 18, 4579-4589 (1999).
109. Nakatogawa, H. & Ito, K. The ribosomal exit tunnel functions as a discriminating gate. Cell 108, 629-636 (2002).
110. Murakami, A., Nakatogawa, H. & Ito, K. Translation arrest of SecM is essential for the basal and regulated expression of SecA. Proc. Natl Acad. Sci. USA 101, 12330-12335 (2004).
111. McNicholas, P., Salavati, R. & Oliver, D. Dual regulation of Escherichia coli secA translation by distinct upstream elements. J. Mol. Biol. 265, 128-141 (1997).
112. Garza-Sánchez, F., Janssen, B. D. & Hayes, C. S. Prolyl-tRNA(Pro) in the A-site of SecM-arrested ribosomes inhibits the recruitment of transfer-messenger RNA. J. Biol. Chem. 281, 34258-34268 (2006). This study shows that programmed stalls in translation can avoid ribosome rescue mechanisms.
113. Cruz-Vera, L. R., Rajagopal, S., Squires, C. & Yanofsky, C. Features of ribosome-peptidyl-tRNA interactions essential for tryptophan induction of tna operon expression. Mol. Cell 19, 333-343 (2005).
114. Hayes, C. S. & Keiler, K. C. Beyond ribosome rescue: tmRNA and co-translational processes. FEBS Lett. 584, 413-419 (2010).
115. Katz, A., Solden, L., Zou, S. B., Navarre, W. W. & Ibba, M. Molecular evolution of protein-RNA mimicry as a mechanism for translational control. Nucleic Acids Res. 42, 3261-3271 (2014).
116. Roy, H. et al. The tRNA synthetase paralog PoxA modifies elongation factor-P with (R)-β-lysine. Nature Chem. Biol. 7, 667-669 (2011).
117. Blaha, G., Stanley, R. E. & Steitz, T. A. Formation of the first peptide bond: the structure of EF-P bound to the 70S ribosome. Science 325, 966-970 (2009).
118. Peil, L. et al. Distinct XPPX sequence motifs induce ribosome stalling, which is rescued by the translation elongation factor EF-P. Proc. Natl Acad. Sci. USA 110, 15265-15270 (2013). In this study, mass spectrometry was used to identify changes in the proteome caused by EF-P, and the stalling propensities of sequences flanking PP motifs were determined.
119. Starosta, A. L. et al. Translational stalling at polyproline stretches is modulated by the sequence context upstream of the stall site. Nucleic Acids Res. 42, 10711-10719 (2014).
120. Hersch, S. J. et al. Divergent protein motifs direct elongation factor P-mediated translational regulation in Salmonella enterica and Escherichia coli. mBio 4, e00180-13 (2013).
121. Zou, S. B., Roy, H., Ibba, M. & Navarre, W. W. Elongation factor P mediates a novel post-transcriptional regulatory pathway critical for bacterial virulence. Virulence 2, 147-151 (2011).
122. Zou, S. B. et al. Loss of elongation factor P disrupts bacterial outer membrane integrity. J. Bacteriol. 194, 413-425 (2012).
123. Hersch, S. J., Elgamal, S., Katz, A., Ibba, M. & Navarre, W. W. Translation initiation rate determines the impact of ribosome stalling on bacterial protein synthesis. J. Biol. Chem. 289, 28160-28171 (2014). This paper answers the question of why the abundance of some proteins that contain stalling sequences is not affected by the absence of EF-P.
124. Qin, Y. et al. The highly conserved LepA is a ribosomal elongation factor that back-translocates the ribosome. Cell 127, 721-733 (2006).
125. Balakrishnan, R., Oman, K., Shoji, S., Bundschuh, R. & Fredrick, K. The conserved GTPase LepA contributes mainly to translation initiation in Escherichia coli. Nucleic Acids Res. 42, 13370-13383 (2014). This study uses ribosome profiling to show that EF4 does not affect translation stalling.
126. Russell, J. H. & Keiler, K. C. Subcellular localization of a bacterial regulatory RNA. Proc. Natl Acad. Sci. USA 106, 16405-16409 (2009).
127. Keiler, K. C. & Shapiro, L. tmRNA in Caulobacter crescentus is cell cycle regulated by temporally controlled transcription and RNA degradation. J. Bacteriol. 185, 1825-1830 (2003).
128. Baranov, P. V. et al. Diverse bacterial genomes encode an operon of two genes, one of which is an unusual class-I release factor that potentially recognizes atypical mRNA signals other than normal stop codons. Biol. Direct 1, 28 (2006).
129. Yamamoto, H. et al. EF-G and EF4: translocation and back-translocation on the bacterial ribosome. Nature Rev. Microbiol. 12, 89-100 (2014).
130. Gagnon, M. G., Lin, J., Bulkley, D. & Steitz, T. A. Crystal structure of elongation factor 4 bound to a clockwise ratcheted ribosome. Science 345, 684-687 (2014).
131. Liu, H. et al. The conserved protein EF4 (LepA) modulates the elongation cycle of protein synthesis. Proc. Natl Acad. Sci. USA 108, 16223-16228 (2011).
132. Selmer, M. et al. Structure of the 70S ribosome complexed with mRNA and tRNA. Science 313, 1935-1942 (2006).