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

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

Author information

1
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.

Abstract

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.

PMID:
23435381
PMCID:
PMC3618526
DOI:
10.1038/nsmb.2516
[Indexed for MEDLINE]
Free PMC Article

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