Structural basis of NEAT1 lncRNA maturation and menRNA instability.

IF 16.8 1区 生物学 Nature Structural &Molecular Biology Pub Date : 2024-07-18 DOI:10.1038/s41594-024-01361-z
Ilias Skeparnias, Jinwei Zhang
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Abstract

NEAT1 long noncoding RNA orchestrates paraspeckle assembly and impacts tumorigenesis, fertility and immunity. Its maturation requires RNase P cleavage yielding an unstable transfer RNA-like multiple endocrine neoplasia-β tRNA-like transcript (menRNA) due to CCACCA addition. Here we report the crystal structure of human menRNA, which partially mimics tRNAs to drive RNase P and ELAC2 processing. Biophysical analyses uncover an RNA-centric, riboswitch-like mechanism whereby the nascent CCA reshapes the RNA folding landscape and propels a spontaneous conformational isomerization that directs repeat CCA addition, marking the menRNA and defective tRNAs for degradation.

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NEAT1 lncRNA 成熟和 menRNA 不稳定性的结构基础
NEAT1 长非编码 RNA 可协调副颈组装,影响肿瘤发生、生育和免疫。它的成熟需要 RNase P 的裂解,由于 CCACCA 的添加,会产生不稳定的类似转移 RNA 的多发性内分泌肿瘤-β tRNA 样转录物(menRNA)。我们在此报告了人类 menRNA 的晶体结构,它部分模拟 tRNA 驱动 RNase P 和 ELAC2 处理。生物物理分析发现了一种以 RNA 为中心的类似核糖开关的机制,新生的 CCA 重塑了 RNA 的折叠结构,并推动了自发的构象异构化,从而引导重复的 CCA 加成,将 menRNA 和有缺陷的 tRNA 标记为降解。
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来源期刊
Nature Structural &Molecular Biology
Nature Structural &Molecular Biology 生物-生化与分子生物学
自引率
1.80%
发文量
160
期刊介绍: Nature Structural & Molecular Biology is a monthly journal that focuses on the functional and mechanistic understanding of how molecular components in a biological process work together. It serves as an integrated forum for structural and molecular studies. The journal places a strong emphasis on the functional and mechanistic understanding of how molecular components in a biological process work together. Some specific areas of interest include the structure and function of proteins, nucleic acids, and other macromolecules, DNA replication, repair and recombination, transcription, regulation of transcription and translation, protein folding, processing and degradation, signal transduction, and intracellular signaling.
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Publisher Correction: Structure and activation of the RING E3 ubiquitin ligase TRIM72 on the membrane. Author Correction: Structural basis for antibody-mediated NMDA receptor clustering and endocytosis in autoimmune encephalitis. The ribosome termination complex remodels release factor RF3 and ejects GDP. Structural basis of NEAT1 lncRNA maturation and menRNA instability. Author Correction: MYC phase separation selectively modulates the transcriptome.
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