An RNA pseudoknot mediates toxin translation and antitoxin inhibition.

Autor:	Eleftheraki A; Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala 75124, Sweden.; Uppsala Antibiotic Center, Uppsala University, Uppsala 75123, Sweden., Holmqvist E; Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala 75124, Sweden.; Uppsala Antibiotic Center, Uppsala University, Uppsala 75123, Sweden.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jul 02; Vol. 121 (27), pp. e2403063121. Date of Electronic Publication: 2024 Jun 27.
DOI:	10.1073/pnas.2403063121
Abstrakt:	Type I toxin-antitoxin systems (T1TAs) are bipartite bacterial loci encoding a growth-inhibitory toxin and an antitoxin small RNA (sRNA). In many of these systems, the transcribed toxin mRNA is translationally inactive, but becomes translation-competent upon ribonucleolytic processing. The antitoxin sRNA targets the processed mRNA to inhibit its translation. This two-level control mechanism prevents cotranscriptional translation of the toxin and allows its synthesis only when the antitoxin is absent. Contrary to this, we found that the timP mRNA of the timPR T1TA locus does not undergo enzymatic processing. Instead, the full-length timP transcript is both translationally active and can be targeted by the antitoxin TimR. Thus, tight control in this system relies on a noncanonical mechanism. Based on the results from in vitro binding assays, RNA structure probing, and cell-free translation experiments, we suggest that timP mRNA adopts mutually exclusive structural conformations. The active form uniquely possesses an RNA pseudoknot structure which is essential for translation initiation. TimR preferentially binds to the active conformation, which leads to pseudoknot destabilization and inhibited translation. Based on this, we propose a model in which "structural processing" of timP mRNA enables tight inhibition by TimR in nonpermissive conditions, and TimP synthesis only upon TimR depletion. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu