The influence of ricin-mediated rRNA depurination on the translational machinery in vivo - New insight into ricin toxicity

Szajwaj, Monika; Wawiórka, Leszek; Molestak, Eliza; Michalec-Wawiórka, Barbara; Mołoń, Mateusz; Wojda, Iwona; Tchórzewski, Marek

doi:10.1016/j.bbamcr.2019.118554

Cited by 9 publications

(11 citation statements)

References 63 publications

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“…At the same time, protein synthesis, as measured by OPP incorporation, was reduced by 78% ±6.8 and 54% ±10.3 respectively (Figure 1C). This disconnect between ricin-induced protein synthesis arrest and cell death has been reported by others (15,37). This phenomenon was underscored when dTHP-1 and A459 cells were treated with cycloheximide (50 µg/mL), a protein synthesis…”

Section: Accepted Articlesupporting

confidence: 61%

“…This disconnect between ricin‐induced protein synthesis arrest and cell death has been reported by others. 15 , 37 This phenomenon was underscored when dTHP‐1 and A459 cells were treated with cycloheximide (50 µg/ml), a protein synthesis inhibitor that sterically blocks the translocation step of peptide elongation without causing direct ribosome damage. 11 , 38 Protein synthesis in A549 and dTHP‐1 cells was reduced by 82% ±4.4 and 67% ±7.2, respectively, without a significant impact on cell viability (Figure 1B,C ).…”

Section: Resultsmentioning

confidence: 99%

“…No copyright is required Ricin is internalized by a wide variety of cell types and inactivates ribosomes with high efficiency (5). However, the cellular and molecular mechanisms ultimately responsible for triggering programmed cell death in response to ricin intoxication remain elusive, but clearly involve more than SRL depurination alone (15) (37). In this report, we confirmed that dTHP-1 and A459 cells are differentially sensitive to ricin-induced cell death: dTHP-1 cells resemble alveolar macrophages (and Kupffer cells) in being hypersensitive to ricin intoxication, while A459 cells were confirmed to be relatively resistant to toxin-induced killing (18,23).…”

Section: Accepted Articlementioning

confidence: 99%

“…Finally, after RTA had refolded on the cytoplasmic face of the ER membrane, it can in theory depurinate both ER-associated ribosomes and those being recruited to the ER by the signal recognition particle (SRP) system (37). The inability of stalled, depurinated ribosomes to engage with open translocon complexes could permit Ca 2+ leakage and ER disequilibrium (59)(60)(61).…”

Section: Accepted Articlementioning

confidence: 99%

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Differential ER stress as a driver of cell fate following ricin toxin exposure

Peterson-Reynolds

Mantis

2021

FASEB BioAdvances

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Acute respiratory distress syndrome (ARDS) is a lifethreatening complication brought about by a variety of insults ranging from physical injury to viral infection to toxin exposure. One such provocateur is ricin, a type II ribosome-inactivating protein (RIP) or ribotoxin found in castor beans (Ricinus communis). 1-3 Ricin's B subunit (RTB) is a Gal/GalNAc-specific lectin that adheres to glycoproteins and glycolipids on cell surfaces and promotes

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Section: Accepted Articlesupporting

confidence: 61%

Section: Resultsmentioning

confidence: 99%

Section: Accepted Articlementioning

confidence: 99%

Section: Accepted Articlementioning

confidence: 99%

See 2 more Smart Citations

Differential ER stress as a driver of cell fate following ricin toxin exposure

Peterson-Reynolds

Mantis

2021

FASEB BioAdvances

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“…It has been shown that RIPs, for example, ricin (ricin A chain – RTA) [32–35], Shiga toxin 1 (Stx1) [36,37], Shiga toxin 2 (Stx2) [38,39], trichosanthin (TCS) [40–42], and maize RIP [43,44], interact with the ribosomal P‐proteins to depurinate SRL. Binding to the P‐stalk is a critical step facilitating SRL depurination by RIPs and its toxicity [32,45,46]. The site of interaction of RIPs with P‐proteins has been mapped to the C termini of P‐proteins [34,37,40], especially mediated by hydrophobic and electrostatic forces [37,42].…”

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confidence: 99%

Phosphorylation of the conserved C‐terminal domain of ribosomal P‐proteins impairs the mode of interaction with plant toxins

et al. 2021

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The ribosome is subjected to post‐translational modifications, including phosphorylation, that affect its biological activity. Among ribosomal elements, the P‐proteins undergo phosphorylation within the C terminus, the element which interacts with trGTPases or ribosome‐inactivating proteins (RIPs); however, the role of phosphorylation has never been elucidated. Here, we probed the function of phosphorylation on the interaction of P‐proteins with RIPs using the ribosomal P1‐P2 dimer. We determined the kinetic parameters of the interaction with the toxins using biolayer interferometry and microscale thermophoresis. The results present the first mechanistic insight into the function of P‐protein phosphorylation, showing that introduction of a negative charge into the C terminus of P1‐P2 proteins promotes α‐helix formation and decreases the affinity of the P‐proteins for the RIPs.

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Increasing the number of ribosomal uL6 mRNA copies accelerates aging of the budding yeast

et al. 2022

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Background Aging is a biological process from which there is no escape. Diverse factors contribute to aging, most notably cell energy metabolism. Ribosome biogenesis and translation are the two main energy-consuming processes that contribute to longevity. It has repeatedly been shown that translation disorders caused by deletion of ribosomal genes delay aging. However, the effect of increasing the amount of ribosomal proteins has remained elusive. Methods and results We determine the relative level of the uL6A and uL6B mRNA derived from the genome and the plasmid. The appearance of additional copies of plasmid-derived uL6 leads to an increase in uL6A and uL6B derived from the BY4741 genome (mainly form B). The relative amount of mRNA of plasmid form B is several times greater than the amount of mRNA in plasmid form A. The level of mRNA derived from the plasmid is increased many times compared to the mRNA of genomic origin. Additionally, the study indicates that excess of uL6A is a limiting or even harmful factor in the reaction to stressful conditions. Therefore, our hypothesis states that uL6A transcription or mRNA uL6A degradation in yeast cells are tightly regulated. our data clearly demonstrate that aging is accelerated when additional copies of uL6 paralogs appear. Conclusion Overexpression of both uL6A or uL6B accelerates aging in the budding yeast. The level of uL6A mRNA is tightly controlled by yeast cell. The uL6a protein plays a pivotal role in the response to environmental stress, including oxidative and osmotic stress, and thus may fall into the class of moonlighting ribosomal proteins with extra-ribosomal function.

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The influence of ricin-mediated rRNA depurination on the translational machinery in vivo - New insight into ricin toxicity

Cited by 9 publications

References 63 publications

Differential ER stress as a driver of cell fate following ricin toxin exposure

Differential ER stress as a driver of cell fate following ricin toxin exposure

Phosphorylation of the conserved C‐terminal domain of ribosomal P‐proteins impairs the mode of interaction with plant toxins

Increasing the number of ribosomal uL6 mRNA copies accelerates aging of the budding yeast

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