Toxic small alarmone synthetase FaRel2 inhibits translation by pyrophosphorylating tRNA<sup>Gly</sup> and tRNA<sup>Thr</sup>.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39536105.
- Also identified by DOI 10.1126/sciadv.adr9624 and PMC identifier 11559606.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 tRNA<sup>Gly</sup> and tRNA<sup>Thr</sup>. The first, second, fourth, and fifth base pairs of the stem act as the specificity determinants. We show that the toxSASs PhRel2 and CapRel<sup>SJ46</sup> 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.
Medical subject headings
- Protein Biosynthesis