NEAT1 lncRNA 成熟和 menRNA 不稳定性的结构基础

IF 12.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature Structural & Molecular Biology Pub Date : 2024-07-18 DOI:10.1038/s41594-024-01361-z

Ilias Skeparnias, Jinwei Zhang

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引用次数: 0

摘要

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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Structural basis of NEAT1 lncRNA maturation and menRNA instability

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Structural basis of NEAT1 lncRNA maturation and menRNA instability

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. This study reveals the mechanisms of NEAT1 lncRNA maturation and menRNA biogenesis and uncovers an RNA-centric, riboswitch-like mechanism where menRNA drives its own conformational isomerization that directs repeat CCA addition and rapid degradation.

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来源期刊

Nature Structural & Molecular Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOPHYSICS

CiteScore

22.00

自引率

1.80%

发文量

160

审稿时长

3-8 weeks

期刊介绍： Nature Structural & Molecular Biology is a comprehensive platform that combines structural and molecular research. Our journal focuses on exploring the functional and mechanistic aspects of biological processes, emphasizing how molecular components collaborate to achieve a particular function. While structural data can shed light on these insights, our publication does not require them as a prerequisite.