Human vtRNA1-1 levels modulate signaling pathways and regulate apoptosis in human cancer cells

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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.

Original languageEnglish
Article number614
JournalBiomolecules
Volume10
Issue number4
DOIs
Publication statusPublished - Apr 2020

Keywords

  • Apoptosis
  • Non-coding RNA
  • Signaling
  • Vault RNA

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