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

Per Johnsson, Amanda Ackley, Linda Vidarsdottir, Weng Onn Lui, Martin Corcoran, Dan Grandér*, Kevin V. Morris

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

320 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)440-446
Number of pages7
JournalNature Structural and Molecular Biology
Volume20
Issue number4
DOIs
Publication statusPublished - May 2013

Bibliographical note

Funding Information:
The project was supported by: the US National Institute of Allergy and Infectious Disease grants R56 AI096861-01 and P01 AI099783-01 to K.V.M. and National Cancer Institute grant R01 CA151574 and US National Institutes of Health grant R01 CA153124 to P.K. Vogt (supporting K.V.M.); the Swedish Childhood Cancer Foundation, The Swedish Cancer Society, Radiumhemmets Forskningsfonder, the Karolinska Institutet PhD support programme and Vetenskapsrådet to D.G.; and the Erik and Edith Fernstrom Foundation for medical research to P.J. and the Swedish Childhood Cancer Foundation.

Fingerprint

Dive into the research topics of 'A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells'. Together they form a unique fingerprint.

Cite this