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

Biomolecules. 2020 Apr 16;10(4):614. doi: 10.3390/biom10040614.


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.

Keywords: apoptosis; non-coding RNA; signaling; vault RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • 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
  • RNA, Untranslated / metabolism*
  • Signal Transduction / genetics*
  • Starvation


  • Nucleotides
  • RNA, Messenger
  • RNA, Untranslated
  • Proto-Oncogene Proteins c-akt