RNA toxins: mediators of stress adaptation and pathogen defense

Abstract

RNA toxins are a group of enzymes primarily synthesized by bacteria, fungi, and plants that either cleave or depurinate RNA molecules. These proteins may be divided according to their RNA substrates: ribotoxins are nucleases that cleave ribosomal RNA (rRNA), ribosome inactivating proteins are glycosidases that remove a base from rRNA, messenger RNA (mRNA) interferases are nucleases that cleave mRNAs, and anticodon nucleases cleave transfer RNAs (tRNAs). These modifications to the RNAs may substantially alter gene expression and translation rates. Given that some of these enzymes cause cell death, it has been suggested that they function mainly in defense, either to kill competing cells or to elicit suicide and thereby limit pathogen spread from infected cells. Although good correlations have been drawn between their enzymatic functions and toxicity, recent work has shown that some RNA toxins cause apoptosis in the absence of damage to RNA and that defense against pathogens can be achieved without host cell death. Moreover, a decrease in cellular translation rate, insufficient to cause cell death, allows some organisms to adapt to stress and environmental change. Although ascribing effects observed in vitro to the roles of these toxins in nature has been challenging, recent results have expanded our understanding of their modes of action, and emphasized the importance of these toxins in development, adaptation to stress and defense against pathogens.

RNAs, Phase Separation, and Membrane‐Less Organelles: Are Post‐Transcriptional Modifications Modulating Organelle Dynamics?

“…In addition, particular RNA modifications can affect the efficiency of RNA processing activities, such as endo-nucleolytic cleavage by ribonucleases, which are often stress-induced ( Figure 2). [105,130,131] Furthermore, 2 0 -O-me can shield RNA against 2 0 -OH-mediated nucleophilic attack on the phosphate backbone thereby stabilizing RNAs. [109] These findings support the notion that specific and "strategically placed" RNA modifications can affect the extent of RNA processing and degradation with implications for the material properties of BioMCs.…”

Battle against RNA oxidation: molecular mechanisms for reducing oxidized RNA to protect cells

“…In E. coli , ribosomal RNA is broken down during starvation in a way similar to mRNA decay . Massive mRNA degradation in E. coli can be carried out by ribotoxins activated by stress . Stress may induce RNA inactivation or decay in eukaryotic cells by the formation of stress granules and P‐bodies, which contain inactivated RNA and many enzymes for RNA degradation .…”

Do the A Subunits Contribute to the Differences in the Toxicity of Shiga Toxin 1 and Shiga Toxin 2?

“…Shiga toxin (Stx) from Shigella dysenteriae and Stx1 (Stx1) and 2 (Stx2) from Shiga toxin-producing Escherichia coli (STEC) are a family of structurally and functionally related proteins [ 5 , 11 ]. Stx, Stx1 and Stx2 are ribosome inactivating proteins (RIPs), a class of proteins that irreversibly damage the ribosome catalytically by modifying the large rRNA and inhibiting protein synthesis [ 12 , 13 , 14 , 15 , 16 ]. RIPs are present throughout the plant kingdom and are also found in bacteria [ 12 , 13 , 14 ].…”

“…Stx, Stx1 and Stx2 are ribosome inactivating proteins (RIPs), a class of proteins that irreversibly damage the ribosome catalytically by modifying the large rRNA and inhibiting protein synthesis [ 12 , 13 , 14 , 15 , 16 ]. RIPs are present throughout the plant kingdom and are also found in bacteria [ 12 , 13 , 14 ]. RIPs are N -glycosidases that remove a specific adenine from the highly conserved α-sarcin/ricin loop (SRL) in the 28S rRNA of the large ribosomal subunit [ 12 , 13 , 14 ].…”

“…RIPs are present throughout the plant kingdom and are also found in bacteria [ 12 , 13 , 14 ]. RIPs are N -glycosidases that remove a specific adenine from the highly conserved α-sarcin/ricin loop (SRL) in the 28S rRNA of the large ribosomal subunit [ 12 , 13 , 14 ]. Irreversible modification of the target adenine blocks elongation factor (EF)-1- and EF-2-dependent GTPase activity and renders the ribosome unable to bind EF-2, thereby blocking translation [ 17 , 18 ].…”