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Nuclear localization of the mitochondrial ncRNAs in normal and cancer cells

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Abstract

Background

We have previously shown a differential expression of a family of mitochondrial ncRNAs in normal and cancer cells. Normal proliferating cells and cancer cells express the sense mitochondrial ncRNA (SncmtRNA). In addition, while normal proliferating cells express two antisense mitochondrial ncRNAs (ASncmtRNAs-1 and −2), these transcripts seem to be universally down-regulated in cancer cells. In situ hybridization (ISH) of some normal and cancer tissues reveals nuclear localization of these transcripts suggesting that they are exported from mitochondria.

Methods

FISH and confocal microscopy, in situ digestion with RNase previous to ISH and electron microscopy ISH was employed to confirm the extra-mitochondrial localization of the SncmtRNA and the ASncmtRNAs in normal proliferating and cancer cells of human and mouse.

Results

In normal human kidney and mouse testis the SncmtRNA and the ASncmtRNAs were found outside the organelle and especially localized in the nucleus associated to heterochromatin. In cancer cells, only the SncmtRNA was expressed and was found associated to heterochromatin and nucleoli.

Conclusion

The ubiquitous localization of these mitochondrial transcripts in the nucleus suggests that they are new players in the mitochondrial-nuclear communication pathway or retrograde signaling. Down regulation of the ASncmtRNAs seems to be an important step on neoplastic transformation and cancer progression.

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Acknowledgments

We thank Mr. Alejandro Munizaga, Pontificia Universidad Catolica de Chile, for his excellent help on the electron microscopy analysis of the samples. This work was supported by Millennium Scientific Initiative N° P-77-09 F, Grants DI-34-09/R, DI-31-09/R and DI-28-09/R4, Universidad Andrés Bello, Grant D04I1338, Fondef, Grant 1085210 and Grant 11090060, Fondecyt and the CCTE-PFB16 Program, Conicyt, Chile

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Authors and Affiliations

  1. Andes Biotechnologies SA and Fundación Ciencia para la Vida, Avenida Zanartu 1482, Santiago, Chile

    Jaime Villegas, Veronica A. Burzio, Luciana Oliveira, Claudio Villota, Constanza Lopez, Franko Restovic, Ronny Martinez & Luis O. Burzio

  2. Laboratorio de Biología Celular y Molecular, Facultad de Ciencias Biologicas, Universidad Andrés Bello, Santiago, Chile

    Jaime Villegas, Veronica A. Burzio & Luis O. Burzio

  3. Facultad de Medicina, Universidad Andrés Bello, Republica 252, Santiago, Chile

    Eduardo Landerer & Octavio Castillo

  4. Clínica Indisa, Vitacura, Santiago, Chile

    Octavio Castillo

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  1. Eduardo Landerer
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Correspondence to Luis O. Burzio.

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Landerer, E., Villegas, J., Burzio, V.A. et al. Nuclear localization of the mitochondrial ncRNAs in normal and cancer cells. Cell Oncol. 34, 297–305 (2011). https://doi.org/10.1007/s13402-011-0018-8

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  • DOI: https://doi.org/10.1007/s13402-011-0018-8

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