Nuclear localization of the mitochondrial ncRNAs in normal and cancer cells

Eduardo Landerer, Jaime Villegas, Veronica A. Burzio, Luciana Oliveira, Claudio Villota, Constanza Lopez, Franko Restovic, Ronny Martinez, Octavio Castillo, Luis O. Burzio

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)297-305
Number of pages9
JournalCellular Oncology
Volume34
Issue number4
DOIs
Publication statusPublished - Aug 2011

Keywords

  • Cancer
  • Mitochondria
  • NcRNAs
  • Nuclear localization
  • Retrograde signaling

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Medicine(all)

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