FA-SAT ncRNA interacts with PKM2 protein: depletion of this complex induces a switch from cell proliferation to apoptosis

Cell Mol Life Sci. 2020 Apr;77(7):1371-1386. doi: 10.1007/s00018-019-03234-x. Epub 2019 Jul 25.

Abstract

FA-SAT is a highly conserved satellite DNA sequence transcribed in many Bilateria species. To disclose the cellular and functional profile of FA-SAT non-coding RNAs, a comprehensive experimental approach, including the transcripts location in the cell and in the cell cycle, the identification of its putative protein interactors, and silencing/ectopic expression phenotype analysis, was performed. FA-SAT non-coding RNAs play a nuclear function at the G1 phase of the cell cycle and the interactomic assay showed that the PKM2 protein is the main interactor. The disruption of the FA-SAT non-coding RNA/PKM2 protein complex, by the depletion of either FA-SAT or PKM2, results in the same phenotype-apoptosis, and the ectopic overexpression of FA-SAT did not affect the cell-cycle progression, but promotes the PKM2 nuclear accumulation. Overall, our data first describe the importance of this ribonucleoprotein complex in apoptosis and cell-cycle progression, what foresees a promising novel candidate molecular target for cancer therapy and diagnosis.

Keywords: Apoptosis; FA-SAT; Non-coding RNA; PKM2; Satellite RNA.

MeSH terms

  • Animals
  • Apoptosis*
  • Carrier Proteins / metabolism*
  • Cats
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • HeLa Cells
  • Humans
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Phenotype
  • Protein Binding
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Satellite / genetics
  • RNA, Satellite / metabolism
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / metabolism*

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA, Satellite
  • RNA, Untranslated
  • Thyroid Hormones