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解读核糖体基因中非编码RNA的起源与功能

Interpreting the Origins and Functions of Noncoding RNAs From the Ribosomal Genes.

作者信息

Moss Tom, Sibai Dany S, Lessard Frédéric

机构信息

St-Patrick Research Group in Basic Oncology, Cancer Division of the Quebec University Hospital Research Centre, Laval University, Quebec, Canada.

Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Laval University, Quebec, Canada.

出版信息

J Cell Physiol. 2025 Aug;240(8):e70080. doi: 10.1002/jcp.70080.

DOI:10.1002/jcp.70080
PMID:40765316
Abstract

The Ribosomal DNA (rDNA) in mammals is organised into large clusters of tandem repeats each of which encodes a single 47S precursor for the 18S, 5.8S, and 28S ribosomal RNAs (rRNAs) that is flanked upstream and downstream by an Intergenic Spacer (IGS) originally referred to as the Non-Transcribed Spacer (NTS). However, in certain cells and under certain environmental conditions the IGS has been found to be transcribed at low level to generate a range of "Noncoding" RNAs (ncRNAs). These ncRNAs have been implicated in the regulation of rRNA synthesis, rDNA silencing and protein sequestration in response to environmental and oncogenic stresses and tumour suppression. Here we review data on the generation, regulation and potential functions of these ncRNAs. We suggest that the majority of the ncRNAs originate from a failure of RNA polymerase I transcription termination by the Reb1- and Myb-related transcriptional "road-block" factor TTF1 and link their expression with tumour suppression.

摘要

哺乳动物的核糖体DNA(rDNA)被组织成串联重复的大簇,每个簇编码一个单一的47S前体,用于18S、5.8S和28S核糖体RNA(rRNA),其上游和下游侧翼是一个基因间隔区(IGS),最初称为非转录间隔区(NTS)。然而,在某些细胞和特定环境条件下,已发现IGS会以低水平转录,产生一系列“非编码”RNA(ncRNA)。这些ncRNA与rRNA合成的调控、rDNA沉默以及响应环境和致癌应激及肿瘤抑制的蛋白质隔离有关。在这里,我们综述了关于这些ncRNA的产生、调控和潜在功能的数据。我们认为,大多数ncRNA源于RNA聚合酶I转录终止的失败,这是由与Reb1和Myb相关的转录“路障”因子TTF1导致的,并将它们的表达与肿瘤抑制联系起来。

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本文引用的文献

1
TTF1 control of LncRNA synthesis delineates a tumor suppressor pathway directly regulating the ribosomal RNA genes.TTF1 通过控制长链非编码 RNA 的合成来划定一条直接调控核糖体 RNA 基因的肿瘤抑制途径。
J Cell Physiol. 2024 Aug;239(8):e31303. doi: 10.1002/jcp.31303. Epub 2024 May 19.
2
A working model for the formation of Robertsonian chromosomes.罗氏易位染色体形成的工作模型。
J Cell Sci. 2024 Apr 1;137(7). doi: 10.1242/jcs.261912. Epub 2024 Apr 12.
3
A nucleolar long "non-coding" RNA encodes a novel protein that functions in response to stress.
核仁长“非编码”RNA 编码一种新型蛋白质,该蛋白质在应激反应中发挥作用。
Proc Natl Acad Sci U S A. 2023 Feb 28;120(9):e2221109120. doi: 10.1073/pnas.2221109120. Epub 2023 Feb 22.
4
Regulation of ribosomal RNA gene copy number, transcription and nucleolus organization in eukaryotes.真核生物中核糖体 RNA 基因拷贝数、转录和核仁组织的调控。
Nat Rev Mol Cell Biol. 2023 Jun;24(6):414-429. doi: 10.1038/s41580-022-00573-9. Epub 2023 Feb 2.
5
Replication protein A associates with nucleolar R loops and regulates rRNA transcription and nucleolar morphology.复制蛋白 A 与核仁 R 环结合,调节 rRNA 转录和核仁形态。
Genes Dev. 2021 Dec 1;35(23-24):1579-1594. doi: 10.1101/gad.348858.121. Epub 2021 Nov 24.
6
The human ribosomal DNA array is composed of highly homogenized tandem clusters.人类核糖体 DNA 序列由高度同质化的串联簇组成。
Genome Res. 2021 Nov;31(11):1971-1982. doi: 10.1101/gr.275838.121. Epub 2021 Aug 18.
7
Prevalence and Phenotypic Impact of Robertsonian Translocations.罗伯逊易位的患病率及表型影响
Mol Syndromol. 2021 Mar;12(1):1-11. doi: 10.1159/000512676. Epub 2021 Feb 17.
8
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9
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Annu Rev Biochem. 2020 Jun 20;89:135-158. doi: 10.1146/annurev-biochem-103019-102815. Epub 2019 Dec 9.
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