Chapter 10 : Leaderless mRNAs in the Spotlight: Ancient but Not Outdated!

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In bacteria and archaea, translation initiates with a 30S ribosomal subunit interacting with an initiator tRNA at the ribosome binding site on a canonical mRNA to form a stable translation initiation complex that is primed for elongation. Canonical mRNAs contain both 5′ and 3′ untranslated regions (UTRs) containing information that will influence the stability and translation efficiency of the mRNA. Within the 5′ UTR, these signals can include ribosome recognition regions such as purine-rich Shine-Dalgarno (SD) sequences that are complementary to the anti-SD (aSD) sequence near the 16S rRNA 3′ terminus ( ), AU-rich sequences that interact with ribosomal protein (r-protein) bS1 ( ) and prevent the formation of secondary structures, and enhancer regions. Additionally, 5′ UTRs may contain sequences that can be bound by -acting elements (i.e., proteins, antisense and small regulatory RNAs, or low-molecular-weight effectors) to change secondary structures or block translation initiation regions. Therefore, the regulatory and translation initiation signals are primarily contained within the 5′ UTR. Despite this functional importance of the 5′ UTR, there exists a class of mRNAs that are completely devoid of 5′ UTRs or possess very short 5′ UTRs. These mRNAs lack the SD sequence and any other translational signals and are so named leaderless mRNAs (lmRNAs). Thus, the mechanism underlying their recognition and binding by the translational apparatus is still not entirely elucidated.

Citation: Beck H, Moll I. 2019. Leaderless mRNAs in the Spotlight: Ancient but Not Outdated!, p 155-170. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0016-2017
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Figure 1

Mechanisms leading to the generation of lmRNAs in bacteria. Besides genes that are generally transcribed as lmRNAs, bacteria can generate lmRNAs in response to adverse environmental conditions (i) by activation of alternative promoters, where the transcriptional start point coincides with the A of the AUG start codon; (ii) by cotranscriptional cleavage, when the 5′ UTR is removed by RNases during the process of transcription; or (iii) cotranslationally. Here, the cleavage can be regulated by translating ribosomes that might either protect mRNAs from cleavage or expose specific sites for the processing event by RNases. Cleavage sites and potential RNases are indicated by red spheres and scissors, respectively.

Citation: Beck H, Moll I. 2019. Leaderless mRNAs in the Spotlight: Ancient but Not Outdated!, p 155-170. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0016-2017
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Figure 2

Potential pathways for translation initiation complex (IC) formation on lmRNAs. (A) Schematic showing the main steps during canonical initiation. (B and C) Potential steps during translation initiation on lmRNAs via 30S subunits and 70S monosomes, respectively. r-Proteins bS1 and uS2 are transparent, indicating their dispensability during this process. See text for details.

Citation: Beck H, Moll I. 2019. Leaderless mRNAs in the Spotlight: Ancient but Not Outdated!, p 155-170. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0016-2017
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1. Shine J,, Dalgarno L . 1974. The 3′-terminal sequence of Escherichia coli 16S ribosomal RNA: complementarity to nonsense triplets and ribosome binding sites. Proc Natl Acad Sci U S A 71 : 1342 1346.[PubMed]
2. Komarova AV,, Tchufistova LS,, Dreyfus M,, Boni IV . 2005. AU-rich sequences within 5′ untranslated leaders enhance translation and stabilize mRNA in Escherichia coli. J Bacteriol 187 : 1344 1349.[PubMed]
3. Boni IV,, Isaeva DM,, Musychenko ML,, Tzareva NV . 1991. Ribosome-messenger recognition: mRNA target sites for ribosomal protein S1. Nucleic Acids Res 19 : 155 162.[PubMed]
4. Grill S,, Gualerzi CO,, Londei P,, Bläsi U . 2000. Selective stimulation of translation of leaderless mRNA by initiation factor 2: evolutionary implications for translation. EMBO J 19 : 4101 4110.[PubMed]
5. Chang B,, Halgamuge S,, Tang SL . 2006. Analysis of SD sequences in completed microbial genomes: non-SD-led genes are as common as SD-led genes. Gene 373 : 90 99.[PubMed]
6. Zheng X,, Hu GQ,, She ZS,, Zhu H . 2011. Leaderless genes in bacteria: clue to the evolution of translation initiation mechanisms in prokaryotes. BMC Genomics 12 : 361.[CrossRef][PubMed]
7. Srivastava A,, Gogoi P,, Deka B,, Goswami S,, Kanaujia SP . 2016. In silico analysis of 5′-UTRs highlights the prevalence of Shine-Dalgarno and leaderless-dependent mechanisms of translation initiation in bacteria and archaea, respectively. J Theor Biol 402 : 54 61.[PubMed]
8. Montoya J,, Ojala D,, Attardi G . 1981. Distinctive features of the 5′-terminal sequences of the human mitochondrial mRNAs. Nature 290 : 465 470.[PubMed]
9. Jones CN,, Wilkinson KA,, Hung KT,, Weeks KM,, Spremulli LL . 2008. Lack of secondary structure characterizes the 5′ ends of mammalian mitochondrial mRNAs. RNA 14 : 862 871.[PubMed]
10. Torarinsson E,, Klenk HP,, Garrett RA . 2005. Divergent transcriptional and translational signals in Archaea. Environ Microbiol 7 : 47 54.[PubMed]
11. Tolstrup N,, Sensen CW,, Garrett RA,, Clausen IG . 2000. Two different and highly organized mechanisms of translation initiation in the archaeon Sulfolobus solfataricus. Extremophiles 4 : 175 179.[PubMed]
12. Slupska MM,, King AG,, Fitz-Gibbon S,, Besemer J,, Borodovsky M,, Miller JH . 2001. Leaderless transcripts of the crenarchaeal hyperthermophile Pyrobaculum aerophilum. J Mol Biol 309 : 347 360.[PubMed]
13. Cho S,, Kim MS,, Jeong Y,, Lee BR,, Lee JH,, Kang SG,, Cho BK . 2017. Genome-wide primary transcriptome analysis of H 2-producing archaeon Thermococcus onnurineus NA1. Sci Rep 7 : 43044.[CrossRef][PubMed]
14. Beck HJ,, Fleming IMC,, Janssen GR . 2016. 5′-Terminal AUGs in Escherichia coli mRNAs with Shine-Dalgarno sequences: identification and analysis of their roles in non-canonical translation initiation. PLoS One 11 : e0160144.[CrossRef][PubMed]
15. Sullivan MJ,, Curson AR,, Shearer N,, Todd JD,, Green RT,, Johnston AW . 2011. Unusual regulation of a leaderless operon involved in the catabolism of dimethylsulfoniopropionate in Rhodobacter sphaeroides. PLoS One 6 : e15972.[CrossRef][PubMed]
16. Tang W,, Wu Y,, Li M,, Wang J,, Mei S,, Tang B,, Tang XF . 2016. Alternative translation initiation of a haloarchaeal serine protease transcript containing two in-frame start codons. J Bacteriol 198 : 1892 1901.[PubMed]
17. Vesper O,, Amitai S,, Belitsky M,, Byrgazov K,, Kaberdina AC,, Engelberg-Kulka H,, Moll I . 2011. Selective translation of leaderless mRNAs by specialized ribosomes generated by MazF in Escherichia coli. Cell 147 : 147 157.[PubMed]
18. Sauert M,, Wolfinger MT,, Vesper O,, Müller C,, Byrgazov K,, Moll I . 2016. The MazF-regulon: a toolbox for the post-transcriptional stress response in Escherichia coli. Nucleic Acids Res 44 : 6660 6675.[PubMed]
19. Hussain T,, Llácer JL,, Wimberly BT,, Kieft JS,, Ramakrishnan V . 2016. Large-scale movements of IF3 and tRNA during bacterial translation initiation. Cell 167 : 133 144.e13.[CrossRef][PubMed]
20. Caban K,, Pavlov M,, Ehrenberg M,, Gonzalez RL Jr . 2017. A conformational switch in initiation factor 2 controls the fidelity of translation initiation in bacteria. Nat Commun 8 : 1475.[CrossRef][PubMed]
21. Milón P,, Rodnina MV . 2012. Kinetic control of translation initiation in bacteria. Crit Rev Biochem Mol Biol 47 : 334 348.[PubMed]
22. Milón P,, Maracci C,, Filonava L,, Gualerzi CO,, Rodnina MV . 2012. Real-time assembly landscape of bacterial 30S translation initiation complex. Nat Struct Mol Biol 19 : 609 615.[PubMed]
23. Antoun A,, Pavlov MY,, Lovmar M,, Ehrenberg M . 2006. How initiation factors maximize the accuracy of tRNA selection in initiation of bacterial protein synthesis. Mol Cell 23 : 183 193.[PubMed]
24. Simonetti A,, Marzi S,, Jenner L,, Myasnikov A,, Romby P,, Yusupova G,, Klaholz BP,, Yusupov M . 2009. A structural view of translation initiation in bacteria. Cell Mol Life Sci 66 : 423 436.[PubMed]
25. Antoun A,, Pavlov MY,, Lovmar M,, Ehrenberg M . 2006. How initiation factors tune the rate of initiation of protein synthesis in bacteria. EMBO J 25 : 2539 2550.[PubMed]
26. Dallas A,, Noller HF . 2001. Interaction of translation initiation factor 3 with the 30S ribosomal subunit. Mol Cell 8 : 855 864.
27. Marshall RA,, Aitken CE,, Puglisi JD . 2009. GTP hydrolysis by IF2 guides progression of the ribosome into elongation. Mol Cell 35 : 37 47.[PubMed]
28. Sørensen MA,, Fricke J,, Pedersen S . 1998. Ribosomal protein S1 is required for translation of most, if not all, natural mRNAs in Escherichia coli in vivo. J Mol Biol 280 : 561 569.[PubMed]
29. Byrgazov K,, Grishkovskaya I,, Arenz S,, Coudevylle N,, Temmel H,, Wilson DN,, Djinovic-Carugo K,, Moll I . 2015. Structural basis for the interaction of protein S1 with the Escherichia coli ribosome. Nucleic Acids Res 43 : 661 673.[PubMed]
30. Lauber MA,, Rappsilber J,, Reilly JP . 2012. Dynamics of ribosomal protein S1 on a bacterial ribosome with cross-linking and mass spectrometry. Mol Cell Proteomics 11 : 1965 1976.[PubMed]
31. Qu X,, Lancaster L,, Noller HF,, Bustamante C,, Tinoco I Jr . 2012. Ribosomal protein S1 unwinds double-stranded RNA in multiple steps. Proc Natl Acad Sci U S A 109 : 14458 14463.[PubMed]
32. Van Duin J,, Wijnands R . 1981. The function of ribosomal protein S21 in protein synthesis. Eur J Biochem 118 : 615 619.[PubMed]
33. Backendorf C,, Ravensbergen CJ,, Van der Plas J,, van Boom JH,, Veeneman G,, Van Duin J . 1981. Basepairing potential of the 3′ terminus of 16S RNA: dependence on the functional state of the 30S subunit and the presence of protein S21. Nucleic Acids Res 9 : 1425 1444.[PubMed]
34. Odom OW,, Stöffler G,, Hardesty B . 1984. Movement of the 3′-end of 16 S RNA towards S21 during activation of 30 S ribosomal subunits. FEBS Lett 173 : 155 158.
35. Moll I,, Resch A,, Bläsi U . 1998. Discrimination of 5′-terminal start codons by translation initiation factor 3 is mediated by ribosomal protein S1. FEBS Lett 436 : 213 217.
36. Tedin K,, Resch A,, Bläsi U . 1997. Requirements for ribosomal protein S1 for translation initiation of mRNAs with and without a 5′ leader sequence. Mol Microbiol 25 : 189 199.[PubMed]
37. Shean CS,, Gottesman ME . 1992. Translation of the prophage λ cl transcript. Cell 70 : 513 522.
38. Moll I,, Grill S,, Gründling A,, Bläsi U . 2002. Effects of ribosomal proteins S1, S2 and the DeaD/CsdA DEAD-box helicase on translation of leaderless and canonical mRNAs in Escherichia coli. Mol Microbiol 44 : 1387 1396.[PubMed]
39. Delvillani F,, Papiani G,, Dehò G,, Briani F . 2011. S1 ribosomal protein and the interplay between translation and mRNA decay. Nucleic Acids Res 39 : 7702 7715.[PubMed]
40. Duval M,, Korepanov A,, Fuchsbauer O,, Fechter P,, Haller A,, Fabbretti A,, Choulier L,, Micura R,, Klaholz BP,, Romby P,, Springer M,, Marzi S . 2013. Escherichia coli ribosomal protein S1 unfolds structured mRNAs onto the ribosome for active translation initiation. PLoS Biol 11 : e1001731.[CrossRef][PubMed]
41. Salah P,, Bisaglia M,, Aliprandi P,, Uzan M,, Sizun C,, Bontems F . 2009. Probing the relationship between Gram-negative and Gram-positive S1 proteins by sequence analysis. Nucleic Acids Res 37 : 5578 5588.[PubMed]
42. Byrgazov K,, Manoharadas S,, Kaberdina AC,, Vesper O,, Moll I . 2012. Direct interaction of the N-terminal domain of ribosomal protein S1 with protein S2 in Escherichia coli. PLoS One 7 : e32702.[CrossRef][PubMed]
43. Aseev LV,, Chugunov AO,, Efremov RG,, Boni IV . 2013. A single missense mutation in a coiled-coil domain of Escherichia coli ribosomal protein S2 confers a thermosensitive phenotype that can be suppressed by ribosomal protein S1. J Bacteriol 195 : 95 104.[PubMed]
44. Moll I,, Hirokawa G,, Kiel MC,, Kaji A,, Bläsi U . 2004. Translation initiation with 70S ribosomes: an alternative pathway for leaderless mRNAs. Nucleic Acids Res 32 : 3354 3363.[PubMed]
45. Grill S,, Moll I,, Hasenöhrl D,, Gualerzi CO,, Bläsi U . 2001. Modulation of ribosomal recruitment to 5′-terminal start codons by translation initiation factors IF2 and IF3. FEBS Lett 495 : 167 171.
46. O’Donnell SM,, Janssen GR . 2002. Leaderless mRNAs bind 70S ribosomes more strongly than 30S ribosomal subunits in Escherichia coli. J Bacteriol 184 : 6730 6733.[PubMed]
47. Tedin K,, Moll I,, Grill S,, Resch A,, Graschopf A,, Gualerzi CO,, Bläsi U . 1999. Translation initiation factor 3 antagonizes authentic start codon selection on leaderless mRNAs. Mol Microbiol 31 : 67 77.[PubMed]
48. Maar D,, Liveris D,, Sussman JK,, Ringquist S,, Moll I,, Heredia N,, Kil A,, Bläsi U,, Schwartz I,, Simons RW . 2008. A single mutation in the IF3 N-terminal domain perturbs the fidelity of translation initiation at three levels. J Mol Biol 383 : 937 944.[PubMed]
49. O’Connor M,, Gregory ST,, Rajbhandary UL,, Dahlberg AE . 2001. Altered discrimination of start codons and initiator tRNAs by mutant initiation factor 3. RNA 7 : 969 978.[PubMed]
50. Moazed D,, Samaha RR,, Gualerzi C,, Noller HF . 1995. Specific protection of 16 S rRNA by translational initiation factors. J Mol Biol 248 : 207 210.
51. Howe JG,, Hershey JW . 1983. Initiation factor and ribosome levels are coordinately controlled in Escherichia coli growing at different rates. J Biol Chem 258 : 1954 1959.[PubMed]
52. Liveris D,, Klotsky RA,, Schwartz I . 1991. Growth rate regulation of translation initiation factor IF3 biosynthesis in Escherichia coli. J Bacteriol 173 : 3888 3893.[PubMed]
53. Jones PG,, VanBogelen RA,, Neidhardt FC . 1987. Induction of proteins in response to low temperature in Escherichia coli. J Bacteriol 169 : 2092 2095.[PubMed]
54. Hinnebusch AG . 2017. Structural insights into the mechanism of scanning and start codon recognition in eukaryotic translation initiation. Trends Biochem Sci 42 : 589 611.[PubMed]
55. Balakin AG,, Skripkin EA,, Shatsky IN,, Bogdanov AA,, Belozersky AN . 1992. Unusual ribosome binding properties of mRNA encoding bacteriophage λ repressor. Nucleic Acids Res 20 : 563 571.[PubMed]
56. Udagawa T,, Shimizu Y,, Ueda T . 2004. Evidence for the translation initiation of leaderless mRNAs by the intact 70 S ribosome without its dissociation into subunits in eubacteria. J Biol Chem 279 : 8539 8546.[PubMed]
57. Benelli D,, Maone E,, Londei P . 2003. Two different mechanisms for ribosome/mRNA interaction in archaeal translation initiation. Mol Microbiol 50 : 635 643.[PubMed]
58. Hasenöhrl D,, Fabbretti A,, Londei P,, Gualerzi CO,, Bläsi U . 2009. Translation initiation complex formation in the crenarchaeon Sulfolobus solfataricus. RNA 15 : 2288 2298.[PubMed]
59. Bell SD,, Jackson SP . 1998. Transcription and translation in Archaea: a mosaic of eukaryal and bacterial features. Trends Microbiol 6 : 222 228.
60. Dennis PP . 1997. Ancient ciphers: translation in Archaea. Cell 89 : 1007 1010.
61. La Teana A,, Benelli D,, Londei P,, Bläsi U . 2013. Translation initiation in the crenarchaeon Sulfolobus solfataricus: eukaryotic features but bacterial route. Biochem Soc Trans 41 : 350 355.[PubMed]
62. Benelli D,, Londei P . 2011. Translation initiation in Archaea: conserved and domain-specific features. Biochem Soc Trans 39 : 89 93.[PubMed]
63. Hasenöhrl D,, Benelli D,, Barbazza A,, Londei P,, Bläsi U . 2006. Sulfolobus solfataricus translation initiation factor 1 stimulates translation initiation complex formation. RNA 12 : 674 682.[PubMed]
64. Pedullà N,, Palermo R,, Hasenöhrl D,, Bläsi U,, Cammarano P,, Londei P . 2005. The archaeal eIF2 homologue: functional properties of an ancient translation initiation factor. Nucleic Acids Res 33 : 1804 1812.[PubMed]
65. Arkhipova V,, Stolboushkina E,, Kravchenko O,, Kljashtorny V,, Gabdulkhakov A,, Garber M,, Nikonov S,, Märtens B,, Bläsi U,, Nikonov O . 2015. Binding of the 5′-triphosphate end of mRNA to the γ-subunit of translation initiation factor 2 of the crenarchaeon Sulfolobus solfataricus. J Mol Biol 427 : 3086 3095.[PubMed]
66. Hasenöhrl D,, Lombo T,, Kaberdin V,, Londei P,, Bläsi U . 2008. Translation initiation factor a/eIF2(-γ) counteracts 5′ to 3′ mRNA decay in the archaeon Sulfolobus solfataricus. Proc Natl Acad Sci U S A 105 : 2146 2150.[PubMed]
67. Londei P . 2005. Evolution of translational initiation: new insights from the archaea. FEMS Microbiol Rev 29 : 185 200.[PubMed]
68. Yatime L,, Schmitt E,, Blanquet S,, Mechulam Y . 2004. Functional molecular mapping of archaeal translation initiation factor 2. J Biol Chem 279 : 15984 15993.[PubMed]
69. Benelli D,, Marzi S,, Mancone C,, Alonzi T,, la Teana A,, Londei P . 2009. Function and ribosomal localization of aIF6, a translational regulator shared by archaea and eukarya. Nucleic Acids Res 37 : 256 267.[PubMed]
70. Resch A,, Tedin K,, Gründling A,, Mündlein A,, Bläsi U . 1996. Downstream box-anti-downstream box interactions are dispensable for translation initiation of leaderless mRNAs. EMBO J 15 : 4740 4748.[PubMed]
71. Moll I,, Huber M,, Grill S,, Sairafi P,, Mueller F,, Brimacombe R,, Londei P,, Bläsi U . 2001. Evidence against an interaction between the mRNA downstream box and 16S rRNA in translation initiation. J Bacteriol 183 : 3499 3505.[PubMed]
72. Martin-Farmer J,, Janssen GR . 1999. A downstream CA repeat sequence increases translation from leadered and unleadered mRNA in Escherichia coli. Mol Microbiol 31 : 1025 1038.[PubMed]
73. Brock JE,, Paz RL,, Cottle P,, Janssen GR . 2007. Naturally occurring adenines within mRNA coding sequences affect ribosome binding and expression in Escherichia coli. J Bacteriol 189 : 501 510.[PubMed]
74. Giliberti J,, O’Donnell S,, Etten WJ,, Janssen GR,, Van Etten WJ,, Janssen GR . 2012. A 5′-terminal phosphate is required for stable ternary complex formation and translation of leaderless mRNA in Escherichia coli. RNA 18 : 508 518.[PubMed]
75. Brock JE,, Pourshahian S,, Giliberti J,, Limbach PA,, Janssen GR . 2008. Ribosomes bind leaderless mRNA in Escherichia coli through recognition of their 5′-terminal AUG. RNA 14 : 2159 2169.[PubMed]
76. Van Etten WJ,, Janssen GR . 1998. An AUG initiation codon, not codon-anticodon complementarity, is required for the translation of unleadered mRNA in Escherichia coli. Mol Microbiol 27 : 987 1001.[PubMed]
77. O’Donnell SM,, Janssen GR . 2001. The initiation codon affects ribosome binding and translational efficiency in Escherichia coli of cI mRNA with or without the 5′ untranslated leader. J Bacteriol 183 : 1277 1283.[PubMed]
78. Hering O,, Brenneis M,, Beer J,, Suess B,, Soppa J . 2009. A novel mechanism for translation initiation operates in haloarchaea. Mol Microbiol 71 : 1451 1463.[PubMed]
79. Shell SS,, Wang J,, Lapierre P,, Mir M,, Chase MR,, Pyle MM,, Gawande R,, Ahmad R,, Sarracino DA,, Ioerger TR,, Fortune SM,, Derbyshire KM,, Wade JT,, Gray TA . 2015. Leaderless transcripts and small proteins are common features of the mycobacterial translational landscape. PLoS Genet 11 : e1005641.[CrossRef][PubMed]
80. Krishnan KM,, Van Etten WJ III,, Janssen GR . 2010. Proximity of the start codon to a leaderless mRNA’s 5′ terminus is a strong positive determinant of ribosome binding and expression in Escherichia coli. J Bacteriol 192 : 6482 6485.[PubMed]
81. Wu CJ,, Janssen GR . 1996. Translation of vph mRNA in Streptomyces lividans and Escherichia coli after removal of the 5′ untranslated leader. Mol Microbiol 22 : 339 355.
82. Wu CJ,, Janssen GR . 1997. Expression of a streptomycete leaderless mRNA encoding chloramphenicol acetyltransferase in Escherichia coli. J Bacteriol 179 : 6824 6830.
83. Kohler R,, Mooney RA,, Mills DJ,, Landick R,, Cramer P . 2017. Architecture of a transcribing-translating expressome. Science 356 : 194 197.[PubMed]
84. Schrader JM,, Zhou B,, Li GW,, Lasker K,, Childers WS,, Williams B,, Long T,, Crosson S,, McAdams HH,, Weissman JS,, Shapiro L . 2014. The coding and noncoding architecture of the Caulobacter crescentus genome. PLoS Genet 10 : e1004463.[CrossRef][PubMed]
85. Sartorius-Neef S,, Pfeifer F . 2004. In vivo studies on putative Shine-Dalgarno sequences of the halophilic archaeon Halobacterium salinarum. Mol Microbiol 51 : 579 588.[PubMed]
86. Condò I,, Ciammaruconi A,, Benelli D,, Ruggero D,, Londei P . 1999. cis-Acting signals controlling translational initiation in the thermophilic archaeon Sulfolobus solfataricus. Mol Microbiol 34 : 377 384.[PubMed]
87. Amitai S,, Kolodkin-Gal I,, Hananya-Meltabashi M,, Sacher A,, Engelberg-Kulka H . 2009. Escherichia coli MazF leads to the simultaneous selective synthesis of both “death proteins” and “survival proteins.” PLoS Genet 5 : e1000390.[CrossRef][PubMed]
88. Andreev DE,, Terenin IM,, Dunaevsky YE,, Dmitriev SE,, Shatsky IN . 2006. A leaderless mRNA can bind to mammalian 80S ribosomes and direct polypeptide synthesis in the absence of translation initiation factors. Mol Cell Biol 26 : 3164 3169.[PubMed]
89. Grill S,, Moll I,, Giuliodori AM,, Gualerzi CO,, Bläsi U . 2002. Temperature-dependent translation of leaderless and canonical mRNAs in Escherichia coli. FEMS Microbiol Lett 211 : 161 167.[PubMed]
90. Chin K,, Shean CS,, Gottesman ME . 1993. Resistance of λ cI translation to antibiotics that inhibit translation initiation. J Bacteriol 175 : 7471 7473.[PubMed]
91. de Groot A,, Roche D,, Fernandez B,, Ludanyi M,, Cruveiller S,, Pignol D,, Vallenet D,, Armengaud J,, Blanchard L . 2014. RNA sequencing and proteogenomics reveal the importance of leaderless mRNAs in the radiation-tolerant bacterium Deinococcus deserti. Genome Biol Evol 6 : 932 948.[PubMed]
92. Bouthier de la Tour C,, Blanchard L,, Dulermo R,, Ludanyi M,, Devigne A,, Armengaud J,, Sommer S,, de Groot A . 2015. The abundant and essential HU proteins in Deinococcus deserti and Deinococcus radiodurans are translated from leaderless mRNA. Microbiology 161 : 2410 2422.[PubMed]
93. Baumeister R,, Flache P,, Melefors O,, von Gabain A,, Hillen W . 1991. Lack of a 5′ non-coding region in Tn 1721 encoded tetR mRNA is associated with a low efficiency of translation and a short half-life in Escherichia coli. Nucleic Acids Res 19 : 4595 4600.[PubMed]
94. Jones RL III,, Jaskula JC,, Janssen GR . 1992. In vivo translational start site selection on leaderless mRNA transcribed from the Streptomyces fradiae aph gene. J Bacteriol 174 : 4753 4760.[PubMed]
95. August PR,, Flickinger MC,, Sherman DH . 1994. Cloning and analysis of a locus ( mcr) involved in mitomycin C resistance in Streptomyces lavendulae. J Bacteriol 176 : 4448 4454.[PubMed]
96. Schluenzen F,, Takemoto C,, Wilson DN,, Kaminishi T,, Harms JM,, Hanawa-Suetsugu K,, Szaflarski W,, Kawazoe M,, Shirouzu M,, Nierhaus KH,, Yokoyama S,, Fucini P . 2006. The antibiotic kasugamycin mimics mRNA nucleotides to destabilize tRNA binding and inhibit canonical translation initiation. Nat Struct Mol Biol 13 : 871 878.[PubMed]
97. Schuwirth BS,, Day JM,, Hau CW,, Janssen GR,, Dahlberg AE,, Cate JH,, Vila-Sanjurjo A . 2006. Structural analysis of kasugamycin inhibition of translation. Nat Struct Mol Biol 13 : 879 886.[PubMed]
98. Moll I,, Bläsi U . 2002. Differential inhibition of 30S and 70S translation initiation complexes on leaderless mRNA by kasugamycin. Biochem Biophys Res Commun 297 : 1021 1026.
99. Ikeno S,, Yamane Y,, Ohishi Y,, Kinoshita N,, Hamada M,, Tsuchiya KS,, Hori M . 2000. ABC transporter genes, kasKLM, responsible for self-resistance of a kasugamycin producer strain. J Antibiot (Tokyo) 53 : 373 384.
100. Müller C,, Sokol L,, Vesper O,, Sauert M,, Moll I . 2016. Insights into the stress response triggered by kasugamycin in Escherichia coli. Antibiotics (Basel) 5 : E19.[CrossRef][PubMed]
101. Hazan R,, Sat B,, Engelberg-Kulka H . 2004. Escherichia coli mazEF-mediated cell death is triggered by various stressful conditions. J Bacteriol 186 : 3663 3669.[PubMed]
102. Sat B,, Hazan R,, Fisher T,, Khaner H,, Glaser G,, Engelberg-Kulka H . 2001. Programmed cell death in Escherichia coli: some antibiotics can trigger mazEF lethality. J Bacteriol 183 : 2041 2045.[PubMed]
103. Aizenman E,, Engelberg-Kulka H,, Glaser G . 1996. An Escherichia coli chromosomal “addiction module” regulated by guanosine [corrected] 3′,5′-bispyrophosphate: a model for programmed bacterial cell death. Proc Natl Acad Sci U S A 93 : 6059 6063.[PubMed]
104. Zhang Y,, Zhang J,, Hara H,, Kato I,, Inouye M . 2005. Insights into the mRNA cleavage mechanism by MazF, an mRNA interferase. J Biol Chem 280 : 3143 3150.[PubMed]
105. Temmel H,, Müller C,, Sauert M,, Vesper O,, Reiss A,, Popow J,, Martinez J,, Moll I . 2017. The RNA ligase RtcB reverses MazF-induced ribosome heterogeneity in Escherichia coli. Nucleic Acids Res 45 : 4708 4721.[PubMed]
106. Cortes T,, Schubert OT,, Rose G,, Arnvig KB,, Comas I,, Aebersold R,, Young DB . 2013. Genome-wide mapping of transcriptional start sites defines an extensive leaderless transcriptome in Mycobacterium tuberculosis. Cell Rep 5 : 1121 1131.[PubMed]
107. Schifano JM,, Edifor R,, Sharp JD,, Ouyang M,, Konkimalla A,, Husson RN,, Woychik NA . 2013. Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site. Proc Natl Acad Sci U S A 110 : 8501 8506.[PubMed]
108. Schifano JM,, Vvedenskaya IO,, Knoblauch JG,, Ouyang M,, Nickels BE,, Woychik NA . 2014. An RNA-seq method for defining endoribonuclease cleavage specificity identifies dual rRNA substrates for toxin MazF-mt3. Nat Commun 5 : 3538.[CrossRef][PubMed]
109. Di Martino ML,, Romilly C,, Wagner EG,, Colonna B,, Prosseda G . 2016. One gene and two proteins: a leaderless mRNA supports the translation of a shorter form of the Shigella VirF regulator. mBio 7 : e01860-16.[CrossRef][PubMed]
110. Kochetov AV . 2008. Alternative translation start sites and hidden coding potential of eukaryotic mRNAs. BioEssays 30 : 683 691.[PubMed]
111. Brenneis M,, Hering O,, Lange C,, Soppa J . 2007. Experimental characterization of cis-acting elements important for translation and transcription in halophilic archaea. PLoS Genet 3 : e229.[CrossRef][PubMed]
112. Donà V,, Rodrigue S,, Dainese E,, Palù G,, Gaudreau L,, Manganelli R,, Provvedi R . 2008. Evidence of complex transcriptional, translational, and posttranslational regulation of the extracytoplasmic function sigma factor σ E in Mycobacterium tuberculosis. J Bacteriol 190 : 5963 5971.[PubMed]
113. Rex G,, Surin B,, Besse G,, Schneppe B,, McCarthy JE . 1994. The mechanism of translational coupling in Escherichia coli. Higher order structure in the atpHA mRNA acts as a conformational switch regulating the access of de novo initiating ribosomes. J Biol Chem 269 : 18118 18127.[PubMed]
114. Yamamoto H,, Wittek D,, Gupta R,, Qin B,, Ueda T,, Krause R,, Yamamoto K,, Albrecht R,, Pech M,, Nierhaus KH . 2016. 70S-scanning initiation is a novel and frequent initiation mode of ribosomal translation in bacteria. Proc Natl Acad Sci U S A 113 : E1180 E1189.[PubMed]
115. Beck HJ,, Janssen GR . 2017. Novel translation initiation regulation mechanism in Escherichia coli ptrB mediated by a 5′-terminal AUG. J Bacteriol 199 : e00091-17.[CrossRef][PubMed]
116. Deana A,, Belasco JG . 2005. Lost in translation: the influence of ribosomes on bacterial mRNA decay. Genes Dev 19 : 2526 2533.[PubMed]
117. Eriksen M,, Sneppen K,, Pedersen S,, Mitarai N . 2017. Occlusion of the ribosome binding site connects the translational initiation frequency, mRNA stability and premature transcription termination. Front Microbiol 8 : 362.[CrossRef][PubMed]
118. Li L,, Wang CC . 2004. Capped mRNA with a single nucleotide leader is optimally translated in a primitive eukaryote, Giardia lamblia. J Biol Chem 279 : 14656 14664.[PubMed]
119. Schlüter JP,, Reinkensmeier J,, Barnett MJ,, Lang C,, Krol E,, Giegerich R,, Long SR,, Becker A . 2013. Global mapping of transcription start sites and promoter motifs in the symbiotic α-proteobacterium Sinorhizobium meliloti 1021. BMC Genomics 14 : 156.[CrossRef][PubMed]
120. Qiu Y,, Cho BK,, Park YS,, Lovley D,, Palsson ,, Zengler K . 2010. Structural and operational complexity of the Geobacter sulfurreducens genome. Genome Res 20 : 1304 1311.[PubMed]
121. Porcelli I,, Reuter M,, Pearson BM,, Wilhelm T,, van Vliet AH . 2013. Parallel evolution of genome structure and transcriptional landscape in the Epsilonproteobacteria. BMC Genomics 14 : 616.[CrossRef][PubMed]
122. Dugar G,, Herbig A,, Förstner KU,, Heidrich N,, Reinhardt R,, Nieselt K,, Sharma CM . 2013. High-resolution transcriptome maps reveal strain-specific regulatory features of multiple Campylobacter jejuni isolates. PLoS Genet 9 : e1003495.[CrossRef][PubMed]
123. Romero DA,, Hasan AH,, Lin YF,, Kime L,, Ruiz-Larrabeiti O,, Urem M,, Bucca G,, Mamanova L,, Laing EE,, van Wezel GP,, Smith CP,, Kaberdin VR,, McDowall KJ . 2014. A comparison of key aspects of gene regulation in Streptomyces coelicolor and Escherichia coli using nucleotide-resolution transcription maps produced in parallel by global and differential RNA sequencing. Mol Microbiol 94 : 963 987.[PubMed]
124. Thomason MK,, Bischler T,, Eisenbart SK,, Förstner KU,, Zhang A,, Herbig A,, Nieselt K,, Sharma CM,, Storz G . 2015. Global transcriptional start site mapping using differential RNA sequencing reveals novel antisense RNAs in Escherichia coli. J Bacteriol 197 : 18 28.[PubMed]
125. Seo JH,, Hong JS,, Kim D,, Cho BK,, Huang TW,, Tsai SF,, Palsson BO,, Charusanti P . 2012. Multiple-omic data analysis of Klebsiella pneumoniae MGH 78578 reveals its transcriptional architecture and regulatory features. BMC Genomics 13 : 679.[CrossRef][PubMed]
126. Kröger C,, Dillon SC,, Cameron ADS,, Papenfort K,, Sivasankaran SK,, Hokamp K,, Chao Y,, Sittka A,, Hébrard M,, Händler K,, Colgan A,, Leekitcharoenphon P,, Langridge GC,, Lohan AJ,, Loftus B,, Lucchini S,, Ussery DW,, Dorman CJ,, Thomson NR,, Vogel J,, Hinton JC . 2012. The transcriptional landscape and small RNAs of Salmonella enterica serovar Typhimurium. Proc Natl Acad Sci U S A 109 : E1277 E1286.[PubMed]
127. Alkhateeb RS,, Vorhölter FJ,, Rückert C,, Mentz A,, Wibberg D,, Hublik G,, Niehaus K,, Pühler A . 2016. Genome wide transcription start sites analysis of Xanthomonas campestris pv. campestris B100 with insights into the gum gene cluster directing the biosynthesis of the exopolysaccharide xanthan. J Biotechnol 225 : 18 28.[PubMed]
128. Sahr T,, Rusniok C,, Dervins-Ravault D,, Sismeiro O,, Coppee JY,, Buchrieser C . 2012. Deep sequencing defines the transcriptional map of L. pneumophila and identifies growth phase-dependent regulated ncRNAs implicated in virulence. RNA Biol 9 : 503 519.[PubMed]
129. Venkataramanan KP,, Min L,, Hou S,, Jones SW,, Ralston MT,, Lee KH,, Papoutsakis ET . 2015. Complex and extensive post-transcriptional regulation revealed by integrative proteomic and transcriptomic analysis of metabolite stress response in Clostridium acetobutylicum. Biotechnol Biofuels 8 : 81.[CrossRef][PubMed]
130. Liao Y,, Huang L,, Wang B,, Zhou F,, Pan L . 2015. The global transcriptional landscape of Bacillus amyloliquefaciens XH7 and high-throughput screening of strong promoters based on RNA-seq data. Gene 571 : 252 262.[PubMed]
131. Ignatov D,, Malakho S,, Majorov K,, Skvortsov T,, Apt A,, Azhikina T . 2013. RNA-Seq analysis of Mycobacterium avium non-coding transcriptome. PLoS One 8 : e74209.[CrossRef][PubMed]
132. Schwientek P,, Neshat A,, Kalinowski J,, Klein A,, Rückert C,, Schneiker-Bekel S,, Wendler S,, Stoye J,, Pühler A . 2014. Improving the genome annotation of the acarbose producer Actinoplanes sp. SE50/110 by sequencing enriched 5′-ends of primary transcripts. J Biotechnol 190 : 85 95.[PubMed]
133. Albersmeier A,, Pfeifer-Sancar K,, Rückert C,, Kalinowski J . 2017. Genome-wide determination of transcription start sites reveals new insights into promoter structures in the actinomycete Corynebacterium glutamicum. J Biotechnol 257 : 99 109.[PubMed]
134. Pfeifer-Sancar K,, Mentz A,, Rückert C,, Kalinowski J . 2013. Comprehensive analysis of the Corynebacterium glutamicum transcriptome using an improved RNAseq technique. BMC Genomics 14 : 888.[CrossRef][PubMed]
135. Bauer JS,, Fillinger S,, Förstner K,, Herbig A,, Jones AC,, Flinspach K,, Sharma C,, Gross H,, Nieselt K,, Apel AK . 2017. dRNA-seq transcriptional profiling of the FK506 biosynthetic gene cluster in Streptomyces tsukubaensis NRRL18488 and general analysis of the transcriptome. RNA Biol 14 : 1617 1626.[PubMed]
136. Voigt K,, Sharma CM,, Mitschke J,, Lambrecht SJ,, Voß B,, Hess WR,, Steglich C . 2014. Comparative transcriptomics of two environmentally relevant cyanobacteria reveals unexpected transcriptome diversity. ISME J 8 : 2056 2068.[PubMed]
137. Babski J,, Haas KA,, Näther-Schindler D,, Pfeiffer F,, Förstner KU,, Hammelmann M,, Hilker R,, Becker A,, Sharma CM,, Marchfelder A,, Soppa J . 2016. Genome-wide identification of transcriptional start sites in the haloarchaeon Haloferax volcanii based on differential RNA-Seq (dRNA-Seq). BMC Genomics 17 : 629.[CrossRef][PubMed]
138. Toffano-Nioche C,, Ott A,, Crozat E,, Nguyen AN,, Zytnicki M,, Leclerc F,, Forterre P,, Bouloc P,, Gautheret D . 2013. RNA at 92°C: the non-coding transcriptome of the hyperthermophilic archaeon Pyrococcus abyssi. RNA Biol 10 : 1211 1220.[PubMed]
139. Wurtzel O,, Sapra R,, Chen F,, Zhu Y,, Simmons BA,, Sorek R . 2010. A single-base resolution map of an archaeal transcriptome. Genome Res 20 : 133 141.[PubMed]


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Table 1

Compilation of published transcriptome analyses outlining the number of leaderless mRNAs in a variety of bacterial and archaeal genomes

Citation: Beck H, Moll I. 2019. Leaderless mRNAs in the Spotlight: Ancient but Not Outdated!, p 155-170. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0016-2017

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