A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by recruiting polycomb proteins

Academic Article

Abstract

  • Long noncoding RNAs (lncRNAs) have emerged as a major regulator of cell physiology, but many of which have no known function. CDKN1A/p21 is an important inhibitor of the cell-cycle, regulator of the DNA damage response and effector of the tumor suppressor p53, playing a crucial role in tumor development and prevention. In order to identify a regulator for tumor progression, we performed an siRNA screen of human lncRNAs required for cell proliferation, and identified a novel lncRNA, APTR, that acts in trans to repress the CDKN1A/p21 promoter independent of p53 to promote cell proliferation. APTR associates with the promoter of CDKN1A/p21 and this association requires a complementary-Alu sequence encoded in APTR. A different module of APTR associates with and recruits the Polycomb repressive complex 2 (PRC2) to epigenetically repress the p21 promoter. A decrease in APTR is necessary for the induction of p21 after heat stress and DNA damage by doxorubicin, and the levels of APTR and p21 are anti-correlated in human glioblastomas. Our data identify a new regulator of the cell-cycle inhibitor CDKN1A/p21 that acts as a proliferative factor in cancer cell lines and in glioblastomas and demonstrate that Alu elements present in lncRNAs can contribute to targeting regulatory lncRNAs to promoters. © 2014 Negishi et al.
  • Published In

  • PLoS One  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 18074159
  • Author List

  • Negishi M; Wongpalee SP; Sarkar S; Park J; Lee KY; Shibata Y; Reon BJ; Abounader R; Suzuki Y; Sugano S
  • Volume

  • 9
  • Issue

  • 4