TERRA RNA与TRF2的结合促进了端粒处异染色质的形成以及ORC的募集。
TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres.
作者信息
Deng Zhong, Norseen Julie, Wiedmer Andreas, Riethman Harold, Lieberman Paul M
机构信息
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
出版信息
Mol Cell. 2009 Aug 28;35(4):403-13. doi: 10.1016/j.molcel.2009.06.025.
Abstract
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.
摘要
端粒重复序列编码RNA（简称为TERRA）已被确定为酵母和哺乳动物端粒的一个潜在组成部分。我们在此表明，TERRA RNA与几种端粒相关蛋白相互作用，包括端粒重复因子1（TRF1）和2（TRF2）、起源识别复合物（ORC）的亚基、异染色质蛋白1（HP1）、组蛋白H3三甲基化赖氨酸9（H3 K9me3）以及DNA损伤感应途径的成员。通过小干扰RNA（siRNA）消耗TERRA会导致端粒功能障碍诱导灶增加、中期端粒畸变，以及端粒重复DNA处组蛋白H3 K9me3和ORC缺失。先前的研究发现，TRF2氨基末端的GAR结构域将ORC招募到端粒。我们现在表明，TERRA RNA可直接与TRF2的GAR和ORC1相互作用，形成稳定的三元复合物。我们得出结论，TERRA促进TRF2与ORC的相互作用，并在端粒结构维持和异染色质形成中发挥核心作用。
相似文献
1
TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres.TERRA RNA与TRF2的结合促进了端粒处异染色质的形成以及ORC的募集。
Mol Cell. 2009 Aug 28;35(4):403-13. doi: 10.1016/j.molcel.2009.06.025.
2
TRF2 recruits ORC through TRFH domain dimerization.TRF2 通过 TRFH 结构域二聚化招募 ORC。
Biochim Biophys Acta Mol Cell Res. 2017 Jan;1864(1):191-201. doi: 10.1016/j.bbamcr.2016.11.004. Epub 2016 Nov 9.
3
TERRA G-quadruplex RNA interaction with TRF2 GAR domain is required for telomere integrity.端粒 G-四链体 RNA 与 TRF2 GAR 结构域的相互作用对于端粒的完整性是必需的。
Sci Rep. 2021 Feb 10;11(1):3509. doi: 10.1038/s41598-021-82406-x.
4
TRF2-mediated ORC recruitment underlies telomere stability upon DNA replication stress.端粒复制应激下，TRF2 介导的 ORC 募集是端粒稳定的基础。
Nucleic Acids Res. 2021 Dec 2;49(21):12234-12251. doi: 10.1093/nar/gkab1004.
5
Involvement of human ORC and TRF2 in pre-replication complex assembly at telomeres.人类ORC和TRF2参与端粒处复制前复合体的组装。
Genes Cells. 2008 Oct;13(10):1045-59. doi: 10.1111/j.1365-2443.2008.01224.x. Epub 2008 Aug 29.
6
BRM-SWI/SNF chromatin remodeling complex enables functional telomeres by promoting co-expression of TRF2 and TRF1.BRM-SWI/SNF 染色质重塑复合物通过促进 TRF2 和 TRF1 的共表达来实现功能端粒。
PLoS Genet. 2020 Jun 5;16(6):e1008799. doi: 10.1371/journal.pgen.1008799. eCollection 2020 Jun.
7
TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres.TIN2同时结合TRF1和TRF2，并在端粒上稳定TRF2复合体。
J Biol Chem. 2004 Nov 5;279(45):47264-71. doi: 10.1074/jbc.M409047200. Epub 2004 Aug 16.
8
The origin recognition complex localizes to telomere repeats and prevents telomere-circle formation.起始识别复合体定位于端粒重复序列并阻止端粒环的形成。
Curr Biol. 2007 Nov 20;17(22):1989-95. doi: 10.1016/j.cub.2007.10.054.
9
Local enrichment of HP1alpha at telomeres alters their structure and regulation of telomere protection.端粒处 HP1alpha 的局部富集改变了端粒的结构和对端粒保护的调控。
Nat Commun. 2018 Sep 4;9(1):3583. doi: 10.1038/s41467-018-05840-y.
10
In Vitro Characterization of the Physical Interactions between the Long Noncoding RNA TERRA and the Telomeric Proteins TRF1 and TRF2.体外鉴定长链非编码 RNA TERRA 与端粒蛋白 TRF1 和 TRF2 的物理相互作用。
Int J Mol Sci. 2022 Sep 9;23(18):10463. doi: 10.3390/ijms231810463.
引用本文的文献
1
Telomeric repeat-containing RNA increases in aged human cells.含端粒重复序列的RNA在衰老的人类细胞中增加。
Nucleic Acids Res. 2025 Jul 8;53(13). doi: 10.1093/nar/gkaf597.
2
Regulation of epigenetics and chromosome structure by human ORC2.人类ORC2对表观遗传学和染色体结构的调控
Cell Rep. 2025 Jun 24;44(6):115816. doi: 10.1016/j.celrep.2025.115816. Epub 2025 Jun 10.
3
Delayed complications of sulfur mustard poisoning: a focus on inflammation and telomere footprint.硫芥中毒的迟发性并发症：聚焦于炎症和端粒印记
Arch Toxicol. 2025 May 7. doi: 10.1007/s00204-025-04033-z.
4
RNAs anchoring replication complex control initiation and firing of DNA replication.锚定复制复合体的RNA控制DNA复制的起始和激发。
Res Sq. 2025 Jan 28:rs.3.rs-5723221. doi: 10.21203/rs.3.rs-5723221/v1.
5
Telomeres: an organized string linking plants and mammals.端粒：连接植物和哺乳动物的有序字符串。
Biol Direct. 2024 Nov 20;19(1):119. doi: 10.1186/s13062-024-00558-y.
6
Telomere transcripts act as tumor suppressor and are associated with favorable prognosis in colorectal cancer with low proliferating cell nuclear antigen expression.端粒转录本具有肿瘤抑制作用，并且与增殖细胞核抗原低表达的结直肠癌患者的良好预后相关。
Cell Oncol (Dordr). 2025 Feb;48(1):239-247. doi: 10.1007/s13402-024-00986-y. Epub 2024 Sep 2.
7
The molecular mechanism for TERRA recruitment and annealing to telomeres.端粒相关 RNA（TERRA）募集和退火到端粒的分子机制。
Nucleic Acids Res. 2024 Sep 23;52(17):10490-10503. doi: 10.1093/nar/gkae732.
8
ORC1 enhances repressive epigenetic modifications on HIV-1 LTR to promote HIV-1 latency.ORC1增强对HIV-1长末端重复序列的抑制性表观遗传修饰，以促进HIV-1潜伏。
J Virol. 2024 Aug 20;98(8):e0003524. doi: 10.1128/jvi.00035-24. Epub 2024 Jul 31.
9
Nesfatin-1 attenuated lipopolysaccharide-induced inflammatory response and senescence in human dental pulp cells.内脂素-1减轻了脂多糖诱导的人牙髓细胞炎症反应和衰老。
Heliyon. 2024 May 31;10(12):e32108. doi: 10.1016/j.heliyon.2024.e32108. eCollection 2024 Jun 30.
10
TERRA transcripts localize at long telomeres to regulate telomerase access to chromosome ends.TERRA 转录本定位于长端粒，以调节端粒酶对染色体末端的访问。
Sci Adv. 2024 Jun 14;10(24):eadk4387. doi: 10.1126/sciadv.adk4387. Epub 2024 Jun 12.
本文引用的文献
1
The Rat1p 5' to 3' exonuclease degrades telomeric repeat-containing RNA and promotes telomere elongation in Saccharomyces cerevisiae.Rat1p 5'至3'核酸外切酶可降解含端粒重复序列的RNA，并促进酿酒酵母中的端粒延长。
Mol Cell. 2008 Nov 21;32(4):465-77. doi: 10.1016/j.molcel.2008.10.019.
2
RNA-dependent recruitment of the origin recognition complex.依赖RNA招募起始识别复合物。
EMBO J. 2008 Nov 19;27(22):3024-35. doi: 10.1038/emboj.2008.221. Epub 2008 Oct 23.
3
Involvement of human ORC and TRF2 in pre-replication complex assembly at telomeres.人类ORC和TRF2参与端粒处复制前复合体的组装。
Genes Cells. 2008 Oct;13(10):1045-59. doi: 10.1111/j.1365-2443.2008.01224.x. Epub 2008 Aug 29.
4
How shelterin protects mammalian telomeres.端粒保护蛋白复合体如何保护哺乳动物的端粒。
Annu Rev Genet. 2008;42:301-34. doi: 10.1146/annurev.genet.41.110306.130350.
5
G-quadruplex formation by human telomeric repeats-containing RNA in Na+ solution.含人端粒重复序列的RNA在钠离子溶液中形成G-四链体。
J Am Chem Soc. 2008 Aug 20;130(33):11179-84. doi: 10.1021/ja8031532. Epub 2008 Jul 19.
6
Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II.由DNA依赖性RNA聚合酶II对哺乳动物端粒进行的发育调控转录。
Nat Cell Biol. 2008 Feb;10(2):228-36. doi: 10.1038/ncb1685. Epub 2007 Dec 23.
7
The origin recognition complex localizes to telomere repeats and prevents telomere-circle formation.起始识别复合体定位于端粒重复序列并阻止端粒环的形成。
Curr Biol. 2007 Nov 20;17(22):1989-95. doi: 10.1016/j.cub.2007.10.054.
8
Transcription and RNAi in heterochromatic gene silencing.转录和 RNAi 在异染色质基因沉默中的作用。
Nat Struct Mol Biol. 2007 Nov;14(11):1041-8. doi: 10.1038/nsmb1315. Epub 2007 Nov 5.
9
An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster.Piwi及一种与Piwi相关的piRNA在黑腹果蝇中的表观遗传激活作用。
Nature. 2007 Nov 8;450(7167):304-8. doi: 10.1038/nature06263. Epub 2007 Oct 21.
10
Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends.哺乳动物染色体末端含端粒重复序列的RNA及RNA监测因子。
Science. 2007 Nov 2;318(5851):798-801. doi: 10.1126/science.1147182. Epub 2007 Oct 4.
Zotero 插件