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.