Essentiality of threonylcarbamoyladenosine (t[superscript 6]A), a universal tRNA modification, in bacteria
Threonylcarbamoyladenosine (t[superscript 6]A) is a modified nucleoside universally conserved in tRNAs in all three kingdoms of life. The recently discovered genes for t6A synthesis, including tsaC and tsaD, are essential in model prokaryotes but not essential in yeast. These genes had been identifi...
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2016
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| Online Access: | http://hdl.handle.net/1721.1/105541 https://orcid.org/0000-0002-4530-5647 |
| _version_ | 1826202925432569856 |
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| author | Thiaville, Patrick C. El Yacoubi, Basma Thiaville, Jennifer J. Deutsch, Chris Iwata-Reuyl, Dirk Bacusmo, Jo Marie Armengaud, Jean Bessho, Yoshitaka Wetzel, Collin Cao, Xiaoyu Limbach, Patrick A. de Crécy-Lagard, Valérie Koehrer, Caroline Rajbhandary, Uttam L |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Thiaville, Patrick C. El Yacoubi, Basma Thiaville, Jennifer J. Deutsch, Chris Iwata-Reuyl, Dirk Bacusmo, Jo Marie Armengaud, Jean Bessho, Yoshitaka Wetzel, Collin Cao, Xiaoyu Limbach, Patrick A. de Crécy-Lagard, Valérie Koehrer, Caroline Rajbhandary, Uttam L |
| author_sort | Thiaville, Patrick C. |
| collection | MIT |
| description | Threonylcarbamoyladenosine (t[superscript 6]A) is a modified nucleoside universally conserved in tRNAs in all three kingdoms of life. The recently discovered genes for t6A synthesis, including tsaC and tsaD, are essential in model prokaryotes but not essential in yeast. These genes had been identified as antibacterial targets even before their functions were known. However, the molecular basis for this prokaryotic-specific essentiality has remained a mystery. Here, we show that t[superscript 6]A is a strong positive determinant for aminoacylation of tRNA by bacterial-type but not by eukaryotic-type isoleucyl-tRNA synthetases and might also be a determinant for the essential enzyme tRNA[superscript Ile]-lysidine synthetase. We confirm that t6A is essential in Escherichia coli and a survey of genomewide essentiality studies shows that genes for t[superscrip 6]A synthesis are essential in most prokaryotes. This essentiality phenotype is not universal in Bacteria as t[superscript 6]A is dispensable in Deinococcus radiodurans, Thermus thermophilus, Synechocystis PCC6803 and Streptococcus mutans. Proteomic analysis of t6A- D. radiodurans strains revealed an induction of the proteotoxic stress response and identified genes whose translation is most affected by the absence of t[superscript 6]A in tRNAs. Thus, although t[superscript 6]A is universally conserved in tRNAs, its role in translation might vary greatly between organisms. |
| first_indexed | 2024-09-23T12:27:03Z |
| format | Article |
| id | mit-1721.1/105541 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:27:03Z |
| publishDate | 2016 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/1055412022-10-01T09:12:45Z Essentiality of threonylcarbamoyladenosine (t[superscript 6]A), a universal tRNA modification, in bacteria Essentiality of threonylcarbamoyladenosine (t6A), a universal tRNA modification, in bacteria Thiaville, Patrick C. El Yacoubi, Basma Thiaville, Jennifer J. Deutsch, Chris Iwata-Reuyl, Dirk Bacusmo, Jo Marie Armengaud, Jean Bessho, Yoshitaka Wetzel, Collin Cao, Xiaoyu Limbach, Patrick A. de Crécy-Lagard, Valérie Koehrer, Caroline Rajbhandary, Uttam L Massachusetts Institute of Technology. Department of Biology Koehrer, Caroline Rajbhandary, Uttam L Threonylcarbamoyladenosine (t[superscript 6]A) is a modified nucleoside universally conserved in tRNAs in all three kingdoms of life. The recently discovered genes for t6A synthesis, including tsaC and tsaD, are essential in model prokaryotes but not essential in yeast. These genes had been identified as antibacterial targets even before their functions were known. However, the molecular basis for this prokaryotic-specific essentiality has remained a mystery. Here, we show that t[superscript 6]A is a strong positive determinant for aminoacylation of tRNA by bacterial-type but not by eukaryotic-type isoleucyl-tRNA synthetases and might also be a determinant for the essential enzyme tRNA[superscript Ile]-lysidine synthetase. We confirm that t6A is essential in Escherichia coli and a survey of genomewide essentiality studies shows that genes for t[superscrip 6]A synthesis are essential in most prokaryotes. This essentiality phenotype is not universal in Bacteria as t[superscript 6]A is dispensable in Deinococcus radiodurans, Thermus thermophilus, Synechocystis PCC6803 and Streptococcus mutans. Proteomic analysis of t6A- D. radiodurans strains revealed an induction of the proteotoxic stress response and identified genes whose translation is most affected by the absence of t[superscript 6]A in tRNAs. Thus, although t[superscript 6]A is universally conserved in tRNAs, its role in translation might vary greatly between organisms. National Institutes of Health (U.S.) (Grant R01 GM17151) 2016-12-02T20:38:51Z 2016-12-02T20:38:51Z 2015-09 2015-08 Article http://purl.org/eprint/type/JournalArticle 0950382X http://hdl.handle.net/1721.1/105541 Thiaville, Patrick C. et al. “Essentiality of Threonylcarbamoyladenosine (T 6 A), a Universal tRNA Modification, in Bacteria: T 6 A Essentiality.” Molecular Microbiology 98.6 (2015): 1199–1221. https://orcid.org/0000-0002-4530-5647 en_US http://dx.doi.org/10.1111/mmi.13209 Molecular Microbiology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC |
| spellingShingle | Thiaville, Patrick C. El Yacoubi, Basma Thiaville, Jennifer J. Deutsch, Chris Iwata-Reuyl, Dirk Bacusmo, Jo Marie Armengaud, Jean Bessho, Yoshitaka Wetzel, Collin Cao, Xiaoyu Limbach, Patrick A. de Crécy-Lagard, Valérie Koehrer, Caroline Rajbhandary, Uttam L Essentiality of threonylcarbamoyladenosine (t[superscript 6]A), a universal tRNA modification, in bacteria |
| title | Essentiality of threonylcarbamoyladenosine (t[superscript 6]A), a universal tRNA modification, in bacteria |
| title_full | Essentiality of threonylcarbamoyladenosine (t[superscript 6]A), a universal tRNA modification, in bacteria |
| title_fullStr | Essentiality of threonylcarbamoyladenosine (t[superscript 6]A), a universal tRNA modification, in bacteria |
| title_full_unstemmed | Essentiality of threonylcarbamoyladenosine (t[superscript 6]A), a universal tRNA modification, in bacteria |
| title_short | Essentiality of threonylcarbamoyladenosine (t[superscript 6]A), a universal tRNA modification, in bacteria |
| title_sort | essentiality of threonylcarbamoyladenosine t superscript 6 a a universal trna modification in bacteria |
| url | http://hdl.handle.net/1721.1/105541 https://orcid.org/0000-0002-4530-5647 |
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