TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres

Mol Cell. 2009 Aug 28;35(4):403-13. doi: 10.1016/j.molcel.2009.06.025.


Telomere-repeat-encoding RNA (referred to as TERRA) has been identified as a potential component of yeast and mammalian telomeres. We show here that TERRA RNA interacts with several telomere-associated proteins, including telomere repeat factors 1 (TRF1) and 2 (TRF2), subunits of the origin recognition complex (ORC), heterochromatin protein 1 (HP1), histone H3 trimethyl K9 (H3 K9me3), and members of the DNA-damage-sensing pathway. siRNA depletion of TERRA caused an increase in telomere dysfunction-induced foci, aberrations in metaphase telomeres, and a loss of histone H3 K9me3 and ORC at telomere repeat DNA. Previous studies found that TRF2 amino-terminal GAR domain recruited ORC to telomeres. We now show that TERRA RNA can interact directly with the TRF2 GAR and ORC1 to form a stable ternary complex. We conclude that TERRA facilitates TRF2 interaction with ORC and plays a central role in telomere structural maintenance and heterochromatin formation.

Publication types

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

MeSH terms

  • Binding Sites
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Aberrations
  • DNA Methylation
  • HCT116 Cells
  • Heterochromatin / metabolism*
  • Histones / metabolism
  • Humans
  • Origin Recognition Complex / metabolism*
  • Protein Structure, Tertiary
  • RNA Interference
  • RNA, Nuclear / metabolism*
  • Telomere / metabolism*
  • Telomere / ultrastructure
  • Telomeric Repeat Binding Protein 1 / metabolism
  • Telomeric Repeat Binding Protein 2 / genetics
  • Telomeric Repeat Binding Protein 2 / metabolism*
  • Time Factors
  • Transfection


  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • Histones
  • Origin Recognition Complex
  • RNA, Nuclear
  • TERF2 protein, human
  • Telomeric Repeat Binding Protein 1
  • Telomeric Repeat Binding Protein 2
  • Chromobox Protein Homolog 5