• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

ASAR lncRNAs 通过与多种 hnRNP/RNA 结合蛋白相互作用来控制 DNA 复制时间。

ASAR lncRNAs control DNA replication timing through interactions with multiple hnRNP/RNA binding proteins.

机构信息

Department of Chemical Physiology and Biochemistry,Oregon Health & Science University, Portland, United States.

Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, United States.

出版信息

Elife. 2024 Jun 18;13:RP95898. doi: 10.7554/eLife.95898.

DOI:10.7554/eLife.95898
PMID:38896448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11186638/
Abstract

ASARs are a family of very-long noncoding RNAs that control replication timing on individual human autosomes, and are essential for chromosome stability. The eight known ASAR lncRNAs remain closely associated with their parent chromosomes. Analysis of RNA-protein interaction data (from ENCODE) revealed numerous RBPs with significant interactions with multiple ASAR lncRNAs, with several hnRNPs as abundant interactors. An ~7 kb domain within the lncRNA shows a striking density of RBP interaction sites. Genetic deletion and ectopic integration assays indicate that this ~7 kb RNA binding protein domain contains functional sequences for controlling replication timing of entire chromosomes in cis. shRNA-mediated depletion of 10 different RNA binding proteins, including HNRNPA1, HNRNPC, HNRNPL, HNRNPM, HNRNPU, or HNRNPUL1, results in dissociation of ASAR lncRNAs from their chromosome territories, and disrupts the synchronous replication that occurs on all autosome pairs, recapitulating the effect of individual ASAR knockouts on a genome-wide scale. Our results further demonstrate the role that ASARs play during the temporal order of genome-wide replication, and we propose that ASARs function as essential RNA scaffolds for the assembly of hnRNP complexes that help maintain the structural integrity of each mammalian chromosome.

摘要

ASARs 是一类非常长的非编码 RNA，它们控制个体人类常染色体的复制时间，是染色体稳定性所必需的。已知的 8 个 ASAR lncRNAs 仍然与其亲本染色体密切相关。对 RNA-蛋白质相互作用数据（来自 ENCODE）的分析揭示了许多与多个 ASAR lncRNAs 有显著相互作用的 RBPs，其中几个 hnRNPs 是丰富的相互作用因子。lncRNA 内的一个约 7kb 区域显示出 RBP 相互作用位点的惊人密度。遗传缺失和异位整合测定表明，这个约 7kb 的 RNA 结合蛋白结构域包含了控制整个染色体在顺式复制时间的功能序列。shRNA 介导的 10 种不同 RNA 结合蛋白（包括 HNRNPA1、HNRNPC、HNRNPL、HNRNPM、HNRNPU 或 HNRNPUL1）的耗竭导致 ASAR lncRNAs 与其染色体领地的分离，并破坏了所有常染色体对同步复制，从而在全基因组范围内再现了单个 ASAR 敲除对基因组的影响。我们的结果进一步证明了 ASARs 在全基因组复制的时间顺序中所起的作用，我们提出 ASARs 作为 hnRNP 复合物组装的必需 RNA 支架，有助于维持每个哺乳动物染色体的结构完整性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/9d870c5644a5/elife-95898-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/143415f4aa2d/elife-95898-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/2624bcb2fda6/elife-95898-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/b18faa2b9fc1/elife-95898-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/d69e82b0e26a/elife-95898-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/781f6e317cbc/elife-95898-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/e4600fa27b83/elife-95898-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/1d6b26a6189b/elife-95898-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/f28b60e6ac59/elife-95898-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/208d837b1b3e/elife-95898-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/6fe5286c49da/elife-95898-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/87779e1f308f/elife-95898-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/f9aa79a85aa5/elife-95898-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/7d837bbace4c/elife-95898-fig6-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/9d870c5644a5/elife-95898-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/143415f4aa2d/elife-95898-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/2624bcb2fda6/elife-95898-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/b18faa2b9fc1/elife-95898-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/d69e82b0e26a/elife-95898-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/781f6e317cbc/elife-95898-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/e4600fa27b83/elife-95898-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/1d6b26a6189b/elife-95898-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/f28b60e6ac59/elife-95898-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/208d837b1b3e/elife-95898-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/6fe5286c49da/elife-95898-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/87779e1f308f/elife-95898-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/f9aa79a85aa5/elife-95898-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/7d837bbace4c/elife-95898-fig6-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb2/11186638/9d870c5644a5/elife-95898-fig7.jpg

相似文献

1
ASAR lncRNAs control DNA replication timing through interactions with multiple hnRNP/RNA binding proteins.ASAR lncRNAs 通过与多种 hnRNP/RNA 结合蛋白相互作用来控制 DNA 复制时间。
Elife. 2024 Jun 18;13:RP95898. doi: 10.7554/eLife.95898.
2
Epigenetic control of chromosome-associated lncRNA genes essential for replication and stability.染色体相关长链非编码 RNA 基因的表观遗传控制对于复制和稳定性至关重要。
Nat Commun. 2022 Oct 22;13(1):6301. doi: 10.1038/s41467-022-34099-7.
3
Reciprocal monoallelic expression of ASAR lncRNA genes controls replication timing of human chromosome 6.ASAR lncRNA 基因的相互单等位基因表达控制人类 6 号染色体的复制时间。
RNA. 2020 Jun;26(6):724-738. doi: 10.1261/rna.073114.119. Epub 2020 Mar 6.
4
L1 retrotransposon antisense RNA within ASAR lncRNAs controls chromosome-wide replication timing.ASAR lncRNAs 内的 L1 反转录转座子反义 RNA 控制着全染色体复制时间。
J Cell Biol. 2018 Feb 5;217(2):541-553. doi: 10.1083/jcb.201707082. Epub 2017 Dec 29.
5
Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation.Spen 连接 RNA 介导的内源性逆转录病毒沉默和 X 染色体失活。
Elife. 2020 May 7;9:e54508. doi: 10.7554/eLife.54508.
6
The NORAD lncRNA assembles a topoisomerase complex critical for genome stability.NORAD lncRNA 组装拓扑异构酶复合物，对于基因组稳定性至关重要。
Nature. 2018 Sep;561(7721):132-136. doi: 10.1038/s41586-018-0453-z. Epub 2018 Aug 27.
7
Functional domains of nuclear long noncoding RNAs: Insights into gene regulation and intracellular architecture.核长非编码 RNA 的功能结构域：对基因调控和细胞内结构的深入了解。
Curr Opin Cell Biol. 2023 Dec;85:102250. doi: 10.1016/j.ceb.2023.102250. Epub 2023 Oct 6.
8
Asynchronous replication, mono-allelic expression, and long range Cis-effects of ASAR6.ASAR6 的非同步复制、单等位基因表达和长距离顺式作用。
PLoS Genet. 2013 Apr;9(4):e1003423. doi: 10.1371/journal.pgen.1003423. Epub 2013 Apr 4.
9
The role of interactions of long non-coding RNAs and heterogeneous nuclear ribonucleoproteins in regulating cellular functions.长链非编码RNA与不均一核核糖核蛋白的相互作用在调节细胞功能中的作用。
Biochem J. 2017 Aug 11;474(17):2925-2935. doi: 10.1042/BCJ20170280.
10
A regulated PNUTS mRNA to lncRNA splice switch mediates EMT and tumour progression.一种受调控的PNUTS信使核糖核酸到长链非编码核糖核酸的剪接开关介导上皮-间质转化和肿瘤进展。
Nat Cell Biol. 2017 Sep;19(9):1105-1115. doi: 10.1038/ncb3595. Epub 2017 Aug 21.

本文引用的文献

1
Epigenetic control of chromosome-associated lncRNA genes essential for replication and stability.染色体相关长链非编码 RNA 基因的表观遗传控制对于复制和稳定性至关重要。
Nat Commun. 2022 Oct 22;13(1):6301. doi: 10.1038/s41467-022-34099-7.
2
40S hnRNP particles are a novel class of nuclear biomolecular condensates.40S 核仁小核糖核蛋白颗粒是一类新型的核生物分子凝聚物。
Nucleic Acids Res. 2022 Jun 24;50(11):6300-6312. doi: 10.1093/nar/gkac457.
3
Long RNA-Mediated Chromatin Regulation in Fission Yeast and Mammals.长 RNA 介导的裂殖酵母和哺乳动物的染色质调控。
Int J Mol Sci. 2022 Jan 16;23(2):968. doi: 10.3390/ijms23020968.
4
SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication.SAF-A 促进起始许可和复制叉前进，以确保强大的 DNA 复制。
J Cell Sci. 2022 Jan 15;135(2). doi: 10.1242/jcs.258991. Epub 2022 Jan 24.
5
SAF-A mutants disrupt chromatin structure through dominant negative effects on RNAs associated with chromatin.SAF-A 突变体通过对与染色质相关的 RNA 产生显性负效应来破坏染色质结构。
Mamm Genome. 2022 Jun;33(2):366-381. doi: 10.1007/s00335-021-09935-8. Epub 2021 Dec 2.
6
Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction.初生 RNA 支架有助于染色体域结构并对抗染色质的紧缩。
Mol Cell. 2021 Sep 2;81(17):3509-3525.e5. doi: 10.1016/j.molcel.2021.07.004. Epub 2021 Jul 27.
7
A protein assembly mediates Xist localization and gene silencing.一种蛋白质复合物介导 Xist 的定位和基因沉默。
Nature. 2020 Nov;587(7832):145-151. doi: 10.1038/s41586-020-2703-0. Epub 2020 Sep 9.
8
Expanded encyclopaedias of DNA elements in the human and mouse genomes.人类和小鼠基因组中 DNA 元件的扩展百科全书。
Nature. 2020 Jul;583(7818):699-710. doi: 10.1038/s41586-020-2493-4. Epub 2020 Jul 29.
9
A large-scale binding and functional map of human RNA-binding proteins.人类 RNA 结合蛋白的大规模结合和功能图谱。
Nature. 2020 Jul;583(7818):711-719. doi: 10.1038/s41586-020-2077-3. Epub 2020 Jul 29.
10
HLTF Promotes Fork Reversal, Limiting Replication Stress Resistance and Preventing Multiple Mechanisms of Unrestrained DNA Synthesis.HLTF 促进叉子反转，限制复制应激抗性并防止无约束 DNA 合成的多种机制。
Mol Cell. 2020 Jun 18;78(6):1237-1251.e7. doi: 10.1016/j.molcel.2020.04.031. Epub 2020 May 21.