title: A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells.
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.
authors: Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
authors: Per
authors: P
authors: Johnsson
authors: Amanda
authors: A
authors: Ackley
authors: Linda
authors: L
authors: Vidarsdottir
authors: Weng-Onn
authors: WO
authors: Lui
authors: Martin
authors: M
authors: Corcoran
authors: Dan
authors: D
authors: Grandér
authors: Kevin V
authors: KV
authors: Morris
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D042002:Chromatin Assembly and Disassembly; D000090205:DNA Methyltransferase 3A; D005786:Gene Expression Regulation / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis / Q000502:physiology*; D011544:Pseudogenes; D022661:RNA, Untranslated / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: C000717967:DNMT3A protein, human; D022661:RNA, Untranslated; D000090205:DNA Methyltransferase 3A; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human