Involvement of telomerase reverse transcriptase in heterochromatin maintenance

Mol Cell Biol. 2014 May;34(9):1576-93. doi: 10.1128/MCB.00093-14. Epub 2014 Feb 18.


In the fission yeast Schizosaccharomyces pombe, centromeric heterochromatin is maintained by an RNA-directed RNA polymerase complex (RDRC) and the RNA-induced transcriptional silencing (RITS) complex in a manner that depends on the generation of short interfering RNA. In association with the telomerase RNA component (TERC), the telomerase reverse transcriptase (TERT) forms telomerase and counteracts telomere attrition, and without TERC, TERT has been implicated in the regulation of heterochromatin at locations distinct from telomeres. Here, we describe a complex composed of human TERT (hTERT), Brahma-related gene 1 (BRG1), and nucleostemin (NS) that contributes to heterochromatin maintenance at centromeres and transposons. This complex produced double-stranded RNAs homologous to centromeric alpha-satellite (alphoid) repeat elements and transposons that were processed into small interfering RNAs targeted to these heterochromatic regions. These small interfering RNAs promoted heterochromatin assembly and mitotic progression in a manner dependent on the RNA interference machinery. These observations implicate the hTERT/BRG1/NS (TBN) complex in heterochromatin assembly at particular sites in the mammalian genome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Centromere / metabolism*
  • DNA Helicases / metabolism*
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Heterochromatin / metabolism*
  • Humans
  • Mitosis
  • Nuclear Proteins / metabolism*
  • RNA / metabolism
  • Retroelements
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / metabolism
  • Telomerase / analysis
  • Telomerase / metabolism*
  • Transcription Factors / metabolism*


  • GNL3 protein, human
  • Heterochromatin
  • Nuclear Proteins
  • Retroelements
  • Schizosaccharomyces pombe Proteins
  • Transcription Factors
  • trt1 protein, S pombe
  • RNA
  • TERT protein, human
  • Telomerase
  • GTP-Binding Proteins
  • SMARCA4 protein, human
  • DNA Helicases