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CD95/Fas ligand mRNA is toxic to cells

CD95/Fas ligand binds to the death receptor CD95 to induce apoptosis in sensitive cells. We previously reported that CD95L mRNA is enriched in sequences that, when converted to si/shRNAs, kill all cancer cells by targeting critical survival genes (Putzbach et al., 2017). We now report expression of...

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Autores principales: Putzbach, Will, Haluck-Kangas, Ashley, Gao, Quan Q, Sarshad, Aishe A, Bartom, Elizabeth T, Stults, Austin, Qadir, Abdul S, Hafner, Markus, Peter, Marcus E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191286/
https://www.ncbi.nlm.nih.gov/pubmed/30324908
http://dx.doi.org/10.7554/eLife.38621
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author Putzbach, Will
Haluck-Kangas, Ashley
Gao, Quan Q
Sarshad, Aishe A
Bartom, Elizabeth T
Stults, Austin
Qadir, Abdul S
Hafner, Markus
Peter, Marcus E
author_facet Putzbach, Will
Haluck-Kangas, Ashley
Gao, Quan Q
Sarshad, Aishe A
Bartom, Elizabeth T
Stults, Austin
Qadir, Abdul S
Hafner, Markus
Peter, Marcus E
author_sort Putzbach, Will
collection PubMed
description CD95/Fas ligand binds to the death receptor CD95 to induce apoptosis in sensitive cells. We previously reported that CD95L mRNA is enriched in sequences that, when converted to si/shRNAs, kill all cancer cells by targeting critical survival genes (Putzbach et al., 2017). We now report expression of full-length CD95L mRNA itself is highly toxic to cells and induces a similar form of cell death. We demonstrate that small (s)RNAs derived from CD95L are loaded into the RNA induced silencing complex (RISC) which is required for the toxicity and processing of CD95L mRNA into sRNAs is independent of both Dicer and Drosha. We provide evidence that in addition to the CD95L transgene a number of endogenous protein coding genes involved in regulating protein translation, particularly under low miRNA conditions, can be processed to sRNAs and loaded into the RISC suggesting a new level of cell fate regulation involving RNAi.
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spelling pubmed-61912862018-10-21 CD95/Fas ligand mRNA is toxic to cells Putzbach, Will Haluck-Kangas, Ashley Gao, Quan Q Sarshad, Aishe A Bartom, Elizabeth T Stults, Austin Qadir, Abdul S Hafner, Markus Peter, Marcus E eLife Cancer Biology CD95/Fas ligand binds to the death receptor CD95 to induce apoptosis in sensitive cells. We previously reported that CD95L mRNA is enriched in sequences that, when converted to si/shRNAs, kill all cancer cells by targeting critical survival genes (Putzbach et al., 2017). We now report expression of full-length CD95L mRNA itself is highly toxic to cells and induces a similar form of cell death. We demonstrate that small (s)RNAs derived from CD95L are loaded into the RNA induced silencing complex (RISC) which is required for the toxicity and processing of CD95L mRNA into sRNAs is independent of both Dicer and Drosha. We provide evidence that in addition to the CD95L transgene a number of endogenous protein coding genes involved in regulating protein translation, particularly under low miRNA conditions, can be processed to sRNAs and loaded into the RISC suggesting a new level of cell fate regulation involving RNAi. eLife Sciences Publications, Ltd 2018-10-16 /pmc/articles/PMC6191286/ /pubmed/30324908 http://dx.doi.org/10.7554/eLife.38621 Text en http://creativecommons.org/publicdomain/zero/1.0/ http://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Cancer Biology
Putzbach, Will
Haluck-Kangas, Ashley
Gao, Quan Q
Sarshad, Aishe A
Bartom, Elizabeth T
Stults, Austin
Qadir, Abdul S
Hafner, Markus
Peter, Marcus E
CD95/Fas ligand mRNA is toxic to cells
title CD95/Fas ligand mRNA is toxic to cells
title_full CD95/Fas ligand mRNA is toxic to cells
title_fullStr CD95/Fas ligand mRNA is toxic to cells
title_full_unstemmed CD95/Fas ligand mRNA is toxic to cells
title_short CD95/Fas ligand mRNA is toxic to cells
title_sort cd95/fas ligand mrna is toxic to cells
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191286/
https://www.ncbi.nlm.nih.gov/pubmed/30324908
http://dx.doi.org/10.7554/eLife.38621
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