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A coding-independent function of gene and pseudogene mRNAs regulates tumour biology.

Nature | 2010

The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction. We find that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the PTENP1 locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. We also demonstrate that the transcripts of protein-coding genes such as PTEN are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.

Pubmed ID: 20577206 RIS Download

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA082328
  • Agency: NCI NIH HHS, United States
    Id: R01 CA-82328-09
  • Agency: NCI NIH HHS, United States
    Id: R01 CA102142
  • Agency: CIHR, Canada
  • Agency: NCI NIH HHS, United States
    Id: R01 CA102142-07

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Gene Expression Omnibus (GEO) (tool)

RRID:SCR_007303

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

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Affymetrix (tool)

RRID:SCR_010231

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 17,2023. Affymetrix is a partially commercial resource that provides DNA Analysis Arrays, Expression Analysis Arrays, Gene Regulation Analysis, and Microarrays. It also provides reagents and assays, instruments, software, and services for a fee. Information is provided for Rats, Humans, and Mice.Affymetrix is now Applied Biosystems, brand of DNA microarray products sold by Thermo Fisher Scientific that originated with an American biotechnology research and development and manufacturing company of the same name.

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Affymetrix (tool)

RRID:SCR_007817

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 17,2023. Affymetrix is a partially commercial resource that provides DNA Analysis Arrays, Expression Analysis Arrays, Gene Regulation Analysis, and Microarrays. It also provides reagents and assays, instruments, software, and services for a fee. Information is provided for Rats, Humans, and Mice.Affymetrix is now Applied Biosystems, brand of DNA microarray products sold by Thermo Fisher Scientific that originated with an American biotechnology research and development and manufacturing company of the same name.

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