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建筑性 NEAT1 非编码 RNA 的分子解剖学:构建相分离核小体 paraspeckles 所需的结构域、相互作用因子和生物发生途径。

Molecular anatomy of the architectural NEAT1 noncoding RNA: The domains, interactors, and biogenesis pathway required to build phase-separated nuclear paraspeckles.

机构信息

Laboratory of RNA Biofucntion, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.

RNA Biology Laboratory, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.

出版信息

Wiley Interdiscip Rev RNA. 2019 Nov;10(6):e1545. doi: 10.1002/wrna.1545. Epub 2019 May 1.


DOI:10.1002/wrna.1545
PMID:31044562
Abstract

Long noncoding RNAs (lncRNAs) are extremely diverse and have various significant physiological functions. lncRNAs generally associate with specific sets of RNA-binding proteins (RBPs) to form functional ribonucleoprotein (RNP) complexes. NEAT1 is a highly abundant lncRNA in the mammalian cell nucleus that associates with specific RBPs to form NEAT1 RNPs. Intriguingly, cellular NEAT1 RNPs are extraordinarily large and can be detected using an optical microscope. These gigantic RNPs, so-called paraspeckles, are a type of membraneless nuclear body. Paraspeckles contain approximately 50 NEAT1 RNA molecules together with characteristic RBPs possessing aggregation-prone prion-like domains. Paraspeckle formation proceeds on the nascent NEAT1 transcript in conjunction with NEAT1 biogenesis, which exhibits various features that differ from those exhibited by mRNA biogenesis, including a lack of introns, noncanonical 3' end formation, and nuclear retention. These unique features may be required for the mechanism of paraspeckle formation. NEAT1 possesses three distinct RNA domains (A, B, and C), which function in stabilization (A), isoform switching (B), and paraspeckle assembly (C). In particular, the central C domain contains smaller subdomains that are high-affinity binding sites for the essential paraspeckle proteins (NONO and SFPQ) that subsequently polymerize along NEAT1. Subsequent recruitment of additional essential PSPs (FUS and RBM14) induces liquid-liquid phase separation to build a massive paraspeckle structure. Thus, the molecular anatomy of the NEAT1 arcRNA provides an ideal model to understand how lncRNAs form the functional RNP machinery. This article is characterized under: RNA Export and Localization > Nuclear Export/Import RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.

摘要

长链非编码 RNA(lncRNA)具有多样性,并具有多种重要的生理功能。lncRNA 通常与特定的 RNA 结合蛋白(RBP)结合,形成功能性核糖核蛋白(RNP)复合物。NEAT1 是哺乳动物细胞核中高度丰富的 lncRNA,它与特定的 RBP 结合,形成 NEAT1 RNP。有趣的是,细胞内的 NEAT1 RNP 非常大,用光学显微镜就可以检测到。这些巨大的 RNP,即所谓的核斑,是一种无膜核体。核斑包含大约 50 个 NEAT1 RNA 分子,以及具有聚集倾向的类朊病毒结构域的特征 RBP。核斑的形成是在新生的 NEAT1 转录本上进行的,同时伴随着 NEAT1 的生物发生,这一过程表现出与 mRNA 生物发生不同的特征,包括缺乏内含子、非典型的 3' 端形成以及核内滞留。这些独特的特征可能是核斑形成的机制所必需的。NEAT1 具有三个不同的 RNA 结构域(A、B 和 C),它们在稳定化(A)、同工型转换(B)和核斑组装(C)中发挥作用。特别是中央 C 结构域包含较小的亚结构域,这些亚结构域是对必需核斑蛋白(NONO 和 SFPQ)的高亲和力结合位点,随后沿 NEAT1 聚合。随后招募额外的必需 PSP(FUS 和 RBM14)诱导液-液相分离,构建一个巨大的核斑结构。因此,NEAT1 弧形 RNA 的分子解剖结构为理解 lncRNA 如何形成功能性 RNP 机制提供了理想的模型。本文的特征在于:RNA 输出和定位>核输出/导入 RNA 与蛋白质和其他分子的相互作用>RNA-蛋白质复合物调控 RNA/RNAi/核酶>调控 RNA RNA 与蛋白质和其他分子的相互作用>蛋白质-RNA 相互作用:功能意义。

相似文献

[1]
Molecular anatomy of the architectural NEAT1 noncoding RNA: The domains, interactors, and biogenesis pathway required to build phase-separated nuclear paraspeckles.

Wiley Interdiscip Rev RNA. 2019-5-1

[2]
Functional Domains of NEAT1 Architectural lncRNA Induce Paraspeckle Assembly through Phase Separation.

Mol Cell. 2018-6-21

[3]
SWI/SNF chromatin-remodeling complexes function in noncoding RNA-dependent assembly of nuclear bodies.

Proc Natl Acad Sci U S A. 2015-4-7

[4]
Organization and function of paraspeckles.

Essays Biochem. 2020-12-7

[5]
Paraspeckle formation during the biogenesis of long non-coding RNAs.

RNA Biol. 2013-1-16

[6]
The building process of the functional paraspeckle with long non-coding RNAs.

Front Biosci (Elite Ed). 2015-1-1

[7]
ARS2 Regulates Nuclear Paraspeckle Formation through 3'-End Processing and Stability of NEAT1 Long Noncoding RNA.

Mol Cell Biol. 2020-1-30

[8]
Identification and characterization of a special type of subnuclear structure: AGGF1-coated paraspeckles.

FASEB J. 2022-6

[9]
Architectural RNAs for Membraneless Nuclear Body Formation.

Cold Spring Harb Symp Quant Biol. 2019

[10]
ALS-linked FUS mutations confer loss and gain of function in the nucleus by promoting excessive formation of dysfunctional paraspeckles.

Acta Neuropathol Commun. 2019-1-14

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