A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells

Nat Struct Mol Biol. 2013 Apr;20(4):440-6. doi: 10.1038/nsmb.2516. Epub 2013 Feb 24.


PTEN is a tumor-suppressor gene that has been shown to be under the regulatory control of a PTEN pseudogene expressed noncoding RNA, PTENpg1. Here, we characterize a previously unidentified PTENpg1-encoded antisense RNA (asRNA), which regulates PTEN transcription and PTEN mRNA stability. We find two PTENpg1 asRNA isoforms, α and β. The α isoform functions in trans, localizes to the PTEN promoter and epigenetically modulates PTEN transcription by the recruitment of DNA methyltransferase 3a and Enhancer of Zeste. In contrast, the β isoform interacts with PTENpg1 through an RNA-RNA pairing interaction, which affects PTEN protein output through changes of PTENpg1 stability and microRNA sponge activity. Disruption of this asRNA-regulated network induces cell-cycle arrest and sensitizes cells to doxorubicin, which suggests a biological function for the respective PTENpg1 expressed asRNAs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Cell Cycle / physiology
  • Chromatin Assembly and Disassembly
  • DNA Methyltransferase 3A
  • Gene Expression Regulation / physiology*
  • Genes, Tumor Suppressor
  • HEK293 Cells
  • Humans
  • PTEN Phosphohydrolase / genetics*
  • Promoter Regions, Genetic
  • Protein Biosynthesis / physiology*
  • Pseudogenes*
  • RNA, Untranslated / genetics
  • RNA, Untranslated / physiology*
  • Transcription, Genetic / physiology*


  • DNMT3A protein, human
  • RNA, Untranslated
  • DNA Methyltransferase 3A
  • PTEN Phosphohydrolase
  • PTEN protein, human