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 (2020). Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells. Biomolecules, 10(4), p. 614. MDPI 10.3390/biom10040614

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
08 Faculty of Science > Departement of Chemistry and Biochemistry

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Bracher, Lisamaria; Ferro, Iolanda; Pulido Quetglas, Carlos; Ruepp, Marc-David; Johnson, Rory Baldwin and Polacek, Norbert

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

2218-273X

Publisher:

MDPI

Language:

English

Submitter:

Christina Schüpbach

Date Deposited:

12 May 2020 15:18

Last Modified:

18 Aug 2020 11:37

Publisher DOI:

10.3390/biom10040614

PubMed ID:

32316166

BORIS DOI:

10.7892/boris.143397

URI:

https://boris.unibe.ch/id/eprint/143397

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