TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres.
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.
Deng
Zhong
Z
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Norseen
Julie
J
Wiedmer
Andreas
A
Riethman
Harold
H
Lieberman
Paul M
PM
D001665:Binding Sites; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002869:Chromosome Aberrations; D019175:DNA Methylation; D045325:HCT116 Cells; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D051738:Origin Recognition Complex / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D015138:RNA, Nuclear / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism* / Q000648:ultrastructure; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D051738:Origin Recognition Complex; D015138:RNA, Nuclear; C504753:TERF2 protein, human; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D000090266:Chromobox Protein Homolog 5