CD95/fas ligand mRNA is toxic to cells

Will Putzbach; Ashley Haluck-Kangas; Quan Q. Gao; Aishe A. Sarshad; Elizabeth T. Bartom; Austin Stults; Abdul S. Qadir; Markus Hafner; Marcus E. Peter

doi:10.7554/eLife.38621

CD95/fas ligand mRNA is toxic to cells

Will Putzbach, Ashley Haluck-Kangas, Quan Q. Gao, Aishe A. Sarshad, Elizabeth T. Bartom, Austin Stults, Abdul S. Qadir, Markus Hafner, Marcus E. Peter^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

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.

Original language	English (US)
Article number	e38621
Journal	eLife
Volume	7
DOIs	https://doi.org/10.7554/eLife.38621
State	Published - Oct 2018

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology
General Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.7554/eLife.38621

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@article{c116bf7bbffd4ae6b47084e9594ee363,

title = "CD95/fas ligand mRNA is toxic to cells",

abstract = "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.",

author = "Will Putzbach and Ashley Haluck-Kangas and Gao, {Quan Q.} and Sarshad, {Aishe A.} and Bartom, {Elizabeth T.} and Austin Stults and Qadir, {Abdul S.} and Markus Hafner and Peter, {Marcus E.}",

year = "2018",

month = oct,

doi = "10.7554/eLife.38621",

language = "English (US)",

volume = "7",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications Ltd",

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TY - JOUR

T1 - CD95/fas ligand mRNA is toxic to cells

AU - Putzbach, Will

AU - Haluck-Kangas, Ashley

AU - Gao, Quan Q.

AU - Sarshad, Aishe A.

AU - Bartom, Elizabeth T.

AU - Stults, Austin

AU - Qadir, Abdul S.

AU - Hafner, Markus

AU - Peter, Marcus E.

PY - 2018/10

Y1 - 2018/10

N2 - 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.

AB - 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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JO - eLife

JF - eLife

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CD95/fas ligand mRNA is toxic to cells

Abstract

ASJC Scopus subject areas

UN SDGs

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