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  • Title: Toxins targeting transfer RNAs: Translation inhibition by bacterial toxin-antitoxin systems.
    Author: Walling LR, Butler JS.
    Journal: Wiley Interdiscip Rev RNA; 2019 Jan; 10(1):e1506. PubMed ID: 30296016.
    Abstract:
    Prokaryotic toxin-antitoxin (TA) systems are composed of a protein toxin and its cognate antitoxin. These systems are abundant in bacteria and archaea and play an important role in growth regulation. During favorable growth conditions, the antitoxin neutralizes the toxin's activity. However, during conditions of stress or starvation, the antitoxin is inactivated, freeing the toxin to inhibit growth and resulting in dormancy. One mechanism of growth inhibition used by several TA systems results from targeting transfer RNAs (tRNAs), either through preventing aminoacylation, acetylating the primary amino group, or endonucleolytic cleavage. All of these mechanisms inhibit translation and result in growth arrest. Many of these toxins only act on a specific tRNA or a specific subset of tRNAs; however, more work is necessary to understand the specificity determinants of these toxins. For the toxins whose specificity has been characterized, both sequence and structural components of the tRNA appear important for recognition by the toxin. Questions also remain regarding the mechanisms used by dormant bacteria to resume growth after toxin induction. Rescue of stalled ribosomes by transfer-messenger RNAs, removal of acetylated amino groups from tRNAs, or ligation of cleaved RNA fragments have all been implicated as mechanisms for reversing toxin-induced dormancy. However, the mechanisms of resuming growth after induction of the majority of tRNA targeting toxins are not yet understood. This article is categorized under: Translation > Translation Regulation RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition.
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