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Article

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

1
Department of Chemistry and Biochemistry, University of Bern, 3012 Bern, Switzerland
2
Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland
3
Department of Medical Oncology, Inselspital, University Hospital and University of Bern, 3010 Bern, Switzerland
4
Department of BioMedical Research, University of Bern, 3008 Bern, Switzerland
5
United Kingdom Dementia Research Institute, King’s College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London SE5 9NU, UK
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(4), 614; https://doi.org/10.3390/biom10040614
Received: 14 March 2020 / Revised: 6 April 2020 / Accepted: 14 April 2020 / Published: 16 April 2020
(This article belongs to the Special Issue Ribonucleoprotein Particles (RNPs): From Structure to Function)
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. View Full-Text
Keywords: non-coding RNA; vault RNA; apoptosis; signaling non-coding RNA; vault RNA; apoptosis; signaling
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MDPI and ACS Style

Bracher, L.; Ferro, I.; Pulido-Quetglas, C.; Ruepp, M.-D.; Johnson, R.; Polacek, N. Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells. Biomolecules 2020, 10, 614. https://doi.org/10.3390/biom10040614

AMA Style

Bracher L, Ferro I, Pulido-Quetglas C, Ruepp M-D, Johnson R, Polacek N. Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells. Biomolecules. 2020; 10(4):614. https://doi.org/10.3390/biom10040614

Chicago/Turabian Style

Bracher, Lisamaria; Ferro, Iolanda; Pulido-Quetglas, Carlos; Ruepp, Marc-David; Johnson, Rory; Polacek, Norbert. 2020. "Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells" Biomolecules 10, no. 4: 614. https://doi.org/10.3390/biom10040614

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