1. Human vtRNA1-1 Levels Modulate Signaling Pathways and Regulate Apoptosis in Human Cancer Cells.
- Author
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Bracher L, Ferro I, Pulido-Quetglas C, Ruepp MD, Johnson R, and Polacek N
- Subjects
- Gene Expression Regulation, Neoplastic, Gene Knockout Techniques, HEK293 Cells, HeLa Cells, High-Throughput Nucleotide Sequencing, Humans, MAP Kinase Signaling System, Nucleotides metabolism, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Untranslated genetics, Starvation, Apoptosis genetics, RNA, Untranslated metabolism, Signal Transduction genetics
- Abstract
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.
- Published
- 2020
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