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PMID: 23435381 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature structural & molecular biology ·Vol. 20 ·No. 4 ·2013-04-00 ·Pages 440-6

Johnsson P, Ackley A, Vidarsdottir L, Lui WO, Corcoran M, Grandér D, Morris KV

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.

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,physiology Transcription, Genetic/physiology
Chemicals
DNMT3A protein, human RNA, Untranslated DNA Methyltransferase 3A PTEN Phosphohydrolase PTEN protein, human
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Johnsson Per
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Ackley Amanda
Vidarsdottir Linda
Lui Weng-Onn
Corcoran Martin
Grandér Dan
Morris Kevin V
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.2516
Published
2013-04-00
Epub
2013-00-24
Pages
440-6
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC3618526
Subset
IM
Grants
NIAID NIH HHS · R56 AI096861-01 · United States
NIAID NIH HHS · P01 AI099783-01 · United States
NIAID NIH HHS · R56 AI096861 · United States
NCI NIH HHS · R01 CA153124 · United States
NCI NIH HHS · R01 CA151574 · United States
NIAID NIH HHS · P01 AI099783 · United States
Corrections
CommentIn
PMID: 23649362
External Links
PubMed source DOI: 10.1038/nsmb.2516 PMC Full Text View journal details
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