A Long Noncoding RNA Regulates Sister Chromatid Cohesion

Mol Cell. 2016 Aug 4;63(3):397-407. doi: 10.1016/j.molcel.2016.06.031. Epub 2016 Jul 28.

Abstract

Long noncoding RNAs (lncRNAs) are involved in diverse cellular processes through multiple mechanisms. Here, we describe a previously uncharacterized human lncRNA, CONCR (cohesion regulator noncoding RNA), that is transcriptionally activated by MYC and is upregulated in multiple cancer types. The expression of CONCR is cell cycle regulated, and it is required for cell-cycle progression and DNA replication. Moreover, cells depleted of CONCR show severe defects in sister chromatid cohesion, suggesting an essential role for CONCR in cohesion establishment during cell division. CONCR interacts with and regulates the activity of DDX11, a DNA-dependent ATPase and helicase involved in DNA replication and sister chromatid cohesion. These findings unveil a direct role for an lncRNA in the establishment of sister chromatid cohesion by modulating DDX11 enzymatic activity.

Publication types

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

MeSH terms

  • A549 Cells
  • Animals
  • Apoptosis
  • Cell Proliferation
  • Chromatids / genetics
  • Chromatids / metabolism*
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Replication*
  • DNA, Neoplasm / biosynthesis*
  • DNA, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • HeLa Cells
  • Humans
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Time Factors
  • Transcription, Genetic
  • Transcriptional Activation
  • Transfection
  • Tumor Burden
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • CONCR long non coding RNA, human
  • DNA, Neoplasm
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • DNA Helicases
  • DDX11 protein, human
  • DEAD-box RNA Helicases