ArticleMolecular biomedicine2023
CD95/Fas ligand mRNA is toxic to cells through more than one mechanism.
Article in Molecular biomedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed, 5 citations in OpenAlex.
- Evolutionary regulation of human Fas ligand (CD95L) by plasmin in solid cancer immunotherapy.Nature communications · 2025Article
- A novel in-vitro expression assay by LC/MS/MS enables multi-antigen mRNA vaccine characterization.Scientific reports · 2025Article
- DISE, an ancient anti-cancer mechanism that senses mutational load in cancerous cells?Oncotarget · 2023Article
- Analysis of the Contribution of 6-mer Seed Toxicity to HIV-1-Induced Cytopathicity.Journal of virology · 2023Article
- CD95/Fas ligand induced toxicity.Biochemical Society transactions · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
CD95/Fas ligand (CD95L) induces apoptosis through protein binding to the CD95 receptor. However, CD95L mRNA also induces toxicity in the absence of CD95 through induction of DISE (Death Induced by Survival Gene Elimination), a form of cell death mediated by RNA interference (RNAi). We now report that CD95L mRNA processing generates a short (s)RNA nearly identical to shL3, a commercial CD95L-targeting shRNA that led to the discovery of DISE. Neither of the miRNA biogenesis proteins Drosha nor Dicer are required for this processing. Interestingly, CD95L toxicity depends on the core component of the RISC, Ago2, in some cell lines, but not in others. In the HCT116 colon cancer cell line, Ago 1-4 appear to function redundantly in RNAi. In fact, Ago 1/2/3 knockout cells retain sensitivity to CD95L mRNA toxicity. Toxicity was only blocked by mutation of all in-frame start codons in the CD95L ORF. Dying cells exhibited an enrichment of RISC bound (R)-sRNAs with toxic 6mer seed sequences, while expression of the non-toxic CD95L mutant enriched for loading of R-sRNAs with nontoxic 6mer seeds. However, CD95L is not the only source of these R-sRNAs. We find that CD95L mRNA may induce DISE directly and indirectly, and that alternate mechanisms may underlie CD95L mRNA processing and toxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.