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A novel long non-coding RNA from NBL2 pericentromeric macrosatellite forms a perinucleolar aggregate structure in

Gabrijela Dumbovic1, Josep Biayna1,2, Jordi Banús1

  • 1Program of Predictive and Personalized Medicine of Cancer (PMPPC), Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, Ctra Can Ruti, camí de les escoles s/n, Badalona, Barcelona 08916, Spain.

Nucleic Acids Research
|June 19, 2018
PubMed

Insights

Primate-specific NBL2 DNA hypomethylation in colorectal cancer (CRC) leads to transcription of novel antisense lncRNAs called TNBL. These TNBL transcripts form structures that interact with nuclear proteins, revealing new cancer-related DNA and RNA features.

Area of Science:

  • Genomics
  • Epigenetics
  • Cancer Biology

Background:

  • The primate-specific NBL2 macrosatellite is hypomethylated in various tumors, but its functional consequences are unknown.
  • NBL2 repeats are located near centromeres and associate with the perinucleolar region.

Purpose of the Study:

  • To investigate the consequences of NBL2 DNA hypomethylation in colorectal cancer (CRC).
  • To identify and characterize novel transcripts arising from NBL2 repeats in cancer.

Main Methods:

  • Analysis of NBL2 methylation status and transcription in CRC cell lines and primary tumors.
  • Identification and characterization of NBL2-derived non-coding RNAs using RNA sequencing.
  • Investigation of TNBL localization, stability, and protein interactions within cancer cells.

Main Results:

  • NBL2 undergoes severe hypomethylation and histone acetylation in a subset of CRCs, leading to its transcription.
  • Novel, non-polyadenylated antisense long non-coding RNAs, designated TNBL, are transcribed from NBL2 monomers.
  • TNBL transcripts form stable perinucleolar aggregates that interact with SAM68 bodies and bind to nuclear proteins like CELF1 and NPM1.

Conclusions:

  • NBL2 hypomethylation in cancer drives the expression of functional antisense lncRNAs (TNBL).
  • TNBL exhibits unique structural and localization properties within the cancer cell nucleus.
  • These findings reveal novel DNA and RNA structural features of a macrosatellite frequently altered in cancer.

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