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Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells

Regulatory non-protein coding RNAs perform a remarkable variety of complex biological functions. Previously, we demonstrated a role of the human non-coding vault RNA1-1 (vtRNA1-1) in inhibiting intrinsic and extrinsic apoptosis in several cancer cell lines. Yet on the molecular level, the function o...

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Autores principales: Bracher, Lisamaria, Ferro, Iolanda, Pulido-Quetglas, Carlos, Ruepp, Marc-David, Johnson, Rory, Polacek, Norbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226377/
https://www.ncbi.nlm.nih.gov/pubmed/32316166
http://dx.doi.org/10.3390/biom10040614
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author Bracher, Lisamaria
Ferro, Iolanda
Pulido-Quetglas, Carlos
Ruepp, Marc-David
Johnson, Rory
Polacek, Norbert
author_facet Bracher, Lisamaria
Ferro, Iolanda
Pulido-Quetglas, Carlos
Ruepp, Marc-David
Johnson, Rory
Polacek, Norbert
author_sort Bracher, Lisamaria
collection PubMed
description Regulatory non-protein coding RNAs perform a remarkable variety of complex biological functions. Previously, we demonstrated a role of the human non-coding vault RNA1-1 (vtRNA1-1) in inhibiting intrinsic and extrinsic apoptosis in several cancer cell lines. Yet on the molecular level, the function of the vtRNA1-1 is still not fully clear. Here, we created HeLa knock-out cell lines revealing that prolonged starvation triggers elevated levels of apoptosis in the absence of vtRNA1-1 but not in vtRNA1-3 knock-out cells. Next-generation deep sequencing of the mRNome identified the PI3K/Akt pathway and the ERK1/2 MAPK cascade, two prominent signaling axes, to be misregulated in the absence of vtRNA1-1 during starvation-mediated cell death conditions. Expression of vtRNA1-1 mutants identified a short stretch of 24 nucleotides of the vtRNA1-1 central domain as being essential for successful maintenance of apoptosis resistance. This study describes a cell signaling-dependent contribution of the human vtRNA1-1 to starvation-induced programmed cell death.
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spelling pubmed-72263772020-05-18 Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells Bracher, Lisamaria Ferro, Iolanda Pulido-Quetglas, Carlos Ruepp, Marc-David Johnson, Rory Polacek, Norbert Biomolecules Article Regulatory non-protein coding RNAs perform a remarkable variety of complex biological functions. Previously, we demonstrated a role of the human non-coding vault RNA1-1 (vtRNA1-1) in inhibiting intrinsic and extrinsic apoptosis in several cancer cell lines. Yet on the molecular level, the function of the vtRNA1-1 is still not fully clear. Here, we created HeLa knock-out cell lines revealing that prolonged starvation triggers elevated levels of apoptosis in the absence of vtRNA1-1 but not in vtRNA1-3 knock-out cells. Next-generation deep sequencing of the mRNome identified the PI3K/Akt pathway and the ERK1/2 MAPK cascade, two prominent signaling axes, to be misregulated in the absence of vtRNA1-1 during starvation-mediated cell death conditions. Expression of vtRNA1-1 mutants identified a short stretch of 24 nucleotides of the vtRNA1-1 central domain as being essential for successful maintenance of apoptosis resistance. This study describes a cell signaling-dependent contribution of the human vtRNA1-1 to starvation-induced programmed cell death. MDPI 2020-04-16 /pmc/articles/PMC7226377/ /pubmed/32316166 http://dx.doi.org/10.3390/biom10040614 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bracher, Lisamaria
Ferro, Iolanda
Pulido-Quetglas, Carlos
Ruepp, Marc-David
Johnson, Rory
Polacek, Norbert
Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells
title Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells
title_full Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells
title_fullStr Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells
title_full_unstemmed Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells
title_short Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells
title_sort human vtrna1-1 levels modulate signaling pathways and regulate apoptosis in human cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226377/
https://www.ncbi.nlm.nih.gov/pubmed/32316166
http://dx.doi.org/10.3390/biom10040614
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