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

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.

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Acknowledgements

This work was supported by the PhD Grants (SFRH/BD/80446/2011, SFRH/BD/98122/2013, SFRH/BD/81495/2011) all from the Science and Technology Foundation (FCT) from Portugal and for the projects with the reference PTDC/NEU-NMC/0205/2012, PTDC/NEU-SCC/7051/2014, UID/NEU/04539/2013 and POCI-01-0145-FEDER-007440, also from FCT and co-financed by “COMPETE Programa Operacional Factores de Competitividade” QREN, the European Union (FEDER—Fundo Europeu de Desenvolvimento Regional) and UID/MULTI/04046/2019 Research Unit grant from FCT (to BioISI). We also want to acknowledge to Raúl Pérez (from CITAB, Vila Real) for the technical support in Flow Cytometry, Elsa Logarinho (PI of the Aging and Aneuploidy group from I3S, Porto) for the support in the lentivirus production and Paula Lopes (from BioISI, Vila Real) for the English revision.

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Ferreira, D., Escudeiro, A., Adega, F. et al. FA-SAT ncRNA interacts with PKM2 protein: depletion of this complex induces a switch from cell proliferation to apoptosis. Cell. Mol. Life Sci. 77, 1371–1386 (2020). https://doi.org/10.1007/s00018-019-03234-x

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Keywords

  • FA-SAT
  • Non-coding RNA
  • Satellite RNA
  • PKM2
  • Apoptosis