Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway

Cell Signal. 2013 May;25(5):1086-95. doi: 10.1016/j.cellsig.2013.02.006. Epub 2013 Feb 14.

Abstract

The maintenance of genome integrity is essential for the proper function and survival of all organisms. Human cells have evolved prompt and efficient DNA damage response to eliminate the detrimental effects of DNA lesions. The DNA damage response involves a complex network of processes that detect and repair DNA damage, in which long non-coding RNAs (lncRNAs), a new class of regulatory RNAs, may play important roles. Recent studies have identified a large number of lncRNAs in mammalian transcriptomes. However, little is known about the regulation and function of lncRNAs in the DNA damage response. In the present study, we demonstrate that one specific lncRNA, ANRIL, is transcriptionally up-regulated by the transcription factor E2F1 in an ATM-dependent manner following DNA damage, and elevated levels of ANRIL suppress the expression of INK4a, INK4b and ARF at the late-stage of DNA damage response, allowing the cell to return to normal at the completion of the DNA repair.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism
  • Apoptosis
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Checkpoints
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Cyclin-Dependent Kinase Inhibitor p15 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins / metabolism*
  • E2F1 Transcription Factor / genetics
  • E2F1 Transcription Factor / metabolism*
  • Genetic Loci
  • Humans
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Tumor Suppressor Proteins / metabolism*
  • Up-Regulation

Substances

  • CDKN2B antisense RNA, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA-Binding Proteins
  • E2F1 Transcription Factor
  • RNA, Long Noncoding
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases
  • ADP-Ribosylation Factors