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TP53-inducible putative long noncoding RNAs encode functional polypeptides that suppress cell proliferation.

Wenli Xu1,2, Chang Liu1, Bing Deng1

  • 1MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.

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TP53-regulated long noncoding RNAs (lncRNAs) can encode functional peptides that suppress cell proliferation. This discovery expands the TP53 tumor-suppressor network and offers new cancer therapy targets.

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Area of Science:

  • Molecular Biology
  • Genomics
  • Cancer Research

Background:

  • Long noncoding RNAs (lncRNAs) can encode polypeptides, a novel class of functional molecules.
  • The role of these lncRNA-encoded peptides in the TP53 pathway remains largely unknown.

Purpose of the Study:

  • To investigate if TP53-regulated lncRNAs encode functional peptides.
  • To explore the biological significance of these peptides in human cell lines and their potential role in cancer.

Main Methods:

  • Ribosome profiling and RNA-sequencing (RNA-seq) in HepG2 cells.
  • Mass spectrometry for peptide validation.
  • Functional assays to assess cell proliferation and cell cycle regulation.

Main Results:

  • Identified over 300 novel TP53-regulated lncRNAs, with 15 confirmed to encode peptides.
  • Validated several peptides using mass spectrometry.
  • Demonstrated that TP53-inducible peptides TP53LC02 and TP53LC04 suppress cell proliferation and TP53LC04 regulates the cell cycle in response to DNA damage.

Conclusions:

  • TP53-regulated lncRNAs can encode novel functional peptides.
  • These peptides expand the TP53 tumor-suppressor network.
  • Identified peptides represent potential novel targets for cancer therapy.