TRMP, a p53-inducible long noncoding RNA, regulates G1/S cell cycle progression by modulating IRES-dependent p27 translation

Cell Death Dis. 2018 Aug 30;9(9):886. doi: 10.1038/s41419-018-0884-3.

Abstract

The tumor suppressor p53 plays a pivotal role in the protection against cancer. Increasing evidence suggests that long noncoding RNA (lncRNA) plays an important role in the regulation of the p53 pathway, however, the detailed mechanisms remain to be further elucidated. In this study, we report a new p53-inducible lncRNA that we termed TRMP (TP53-regulated modulator of p27). As a direct transcriptional target of p53, TRMP plays an unexpected pro-survival function. Knockdown of TRMP inhibits cell proliferation by inducing a G1 cell cycle arrest. Mechanistically, TRMP suppresses internal ribosomal entry site (IRES)-dependent translation of p27 by competing p27 mRNA for polypyrimidine tract-binding protein 1 (PTBP1) binding. Furthermore, TRMP is able to regulate cell proliferation, G1/S cell cycle progression, and tumor xenograft growth via the inhibition of p27. Taken together, these findings suggest lncRNA as a new layer to fine-tune the p53 response and reveal TRMP as an important downstream effector of p53 activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • G1 Phase Cell Cycle Checkpoints / genetics*
  • HEK293 Cells
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Polypyrimidine Tract-Binding Protein / metabolism
  • Proliferating Cell Nuclear Antigen / biosynthesis*
  • Proliferating Cell Nuclear Antigen / genetics
  • Protein Biosynthesis / genetics
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Heterogeneous-Nuclear Ribonucleoproteins
  • PTBP1 protein, human
  • Proliferating Cell Nuclear Antigen
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • p27 antigen
  • Polypyrimidine Tract-Binding Protein