Toxic small alarmone synthetase FaRel2 inhibits translation by pyrophosphorylating tRNAGly and tRNAThr
Kurata, Tatsuaki LU ; Takegawa, Masaki ; Ohira, Takayuki ; Syroegin, Egor A ; Atkinson, Gemma C LU
; Johansson, Marcus J O
LU
; Polikanov, Yury S
; Garcia-Pino, Abel
; Suzuki, Tsutomu
and Hauryliuk, Vasili
LU
(2024)
In Science Advances
10(46).
- Abstract
Translation-targeting toxic small alarmone synthetases (toxSAS) are effectors of bacterial toxin-antitoxin systems that pyrophosphorylate the 3'-CCA end of transfer RNA (tRNA) to prevent aminoacylation. toxSAS are implicated in antiphage immunity: Phage detection triggers the toxSAS activity to shut down viral production. We show that the toxSAS FaRel2 inspects the tRNA acceptor stem to specifically select tRNAGly and tRNAThr. The first, second, fourth, and fifth base pairs of the stem act as the specificity determinants. We show that the toxSASs PhRel2 and CapRelSJ46 differ in tRNA specificity from FaRel2 and rationalize this through structural modeling: While the universal 3'-CCA end slots into a highly conserved CCA recognition... (More)
Translation-targeting toxic small alarmone synthetases (toxSAS) are effectors of bacterial toxin-antitoxin systems that pyrophosphorylate the 3'-CCA end of transfer RNA (tRNA) to prevent aminoacylation. toxSAS are implicated in antiphage immunity: Phage detection triggers the toxSAS activity to shut down viral production. We show that the toxSAS FaRel2 inspects the tRNA acceptor stem to specifically select tRNAGly and tRNAThr. The first, second, fourth, and fifth base pairs of the stem act as the specificity determinants. We show that the toxSASs PhRel2 and CapRelSJ46 differ in tRNA specificity from FaRel2 and rationalize this through structural modeling: While the universal 3'-CCA end slots into a highly conserved CCA recognition groove, the acceptor stem recognition region is variable across toxSAS diversity. As phages use tRNA isoacceptors to overcome tRNA-targeting defenses, we hypothesize that highly evolvable modular tRNA recognition allows for the escape of viral countermeasures through tRNA substrate specificity switching.
(Less)
- author
- Kurata, Tatsuaki
LU
; Takegawa, Masaki
; Ohira, Takayuki
; Syroegin, Egor A
; Atkinson, Gemma C
LU
; Johansson, Marcus J O
LU
; Polikanov, Yury S
; Garcia-Pino, Abel
; Suzuki, Tsutomu
and Hauryliuk, Vasili
LU
- organization
- publishing date
- 2024-11-15
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Protein Biosynthesis, Substrate Specificity, RNA, Transfer/metabolism, Models, Molecular, Bacterial Proteins/metabolism, Nucleic Acid Conformation, Ligases/metabolism, Bacteriophages/metabolism, Escherichia coli/metabolism
- in
- Science Advances
- volume
- 10
- issue
- 46
- article number
- eadr9624
- publisher
- American Association for the Advancement of Science (AAAS)
- external identifiers
-
- scopus:85209357402
- pmid:39536105
- ISSN
- 2375-2548
- DOI
- 10.1126/sciadv.adr9624
- project
- För banbrytande studier av hur proteinsyntes regleras i bakterier
- Interrogating bacteriophages to discover the universal secrets of host-virus and virus-virus warfare
- language
- English
- LU publication?
- yes
- id
- 861f6852-f9dc-4ad6-9844-1186f714ed02
- date added to LUP
- 2024-11-15 12:28:58
- date last changed
- 2025-07-09 22:38:46
@article{861f6852-f9dc-4ad6-9844-1186f714ed02,
abstract = {{<p>Translation-targeting toxic small alarmone synthetases (toxSAS) are effectors of bacterial toxin-antitoxin systems that pyrophosphorylate the 3'-CCA end of transfer RNA (tRNA) to prevent aminoacylation. toxSAS are implicated in antiphage immunity: Phage detection triggers the toxSAS activity to shut down viral production. We show that the toxSAS FaRel2 inspects the tRNA acceptor stem to specifically select tRNAGly and tRNAThr. The first, second, fourth, and fifth base pairs of the stem act as the specificity determinants. We show that the toxSASs PhRel2 and CapRelSJ46 differ in tRNA specificity from FaRel2 and rationalize this through structural modeling: While the universal 3'-CCA end slots into a highly conserved CCA recognition groove, the acceptor stem recognition region is variable across toxSAS diversity. As phages use tRNA isoacceptors to overcome tRNA-targeting defenses, we hypothesize that highly evolvable modular tRNA recognition allows for the escape of viral countermeasures through tRNA substrate specificity switching.</p>}},
author = {{Kurata, Tatsuaki and Takegawa, Masaki and Ohira, Takayuki and Syroegin, Egor A and Atkinson, Gemma C and Johansson, Marcus J O and Polikanov, Yury S and Garcia-Pino, Abel and Suzuki, Tsutomu and Hauryliuk, Vasili}},
issn = {{2375-2548}},
keywords = {{Protein Biosynthesis; Substrate Specificity; RNA, Transfer/metabolism; Models, Molecular; Bacterial Proteins/metabolism; Nucleic Acid Conformation; Ligases/metabolism; Bacteriophages/metabolism; Escherichia coli/metabolism}},
language = {{eng}},
month = {{11}},
number = {{46}},
publisher = {{American Association for the Advancement of Science (AAAS)}},
series = {{Science Advances}},
title = {{Toxic small alarmone synthetase FaRel2 inhibits translation by pyrophosphorylating tRNAGly and tRNAThr}},
url = {{http://dx.doi.org/10.1126/sciadv.adr9624}},
doi = {{10.1126/sciadv.adr9624}},
volume = {{10}},
year = {{2024}},
}