Alu RNA假结改变影响SRP9/SRP14的关联。

IF 4.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA Pub Date : 2025-07-16 DOI:10.1261/rna.080359.124
Daniel Gussakovsky, Mira J F Brown, Higor Sette Pereira, Markus Meier, G Pauline Padilla-Meier, Nicole A Black, Evan P Booy, Jörg Stetefeld, Trushar R Patel, Sean A McKenna
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引用次数: 0

摘要

人类基因组中有超过100万个Alu元件,它们可以被转录成离散的、RNA聚合酶III转录的非编码Alu RNA。这些Alu rna经常与蛋白质异源二聚体SRP9/SRP14相互作用并受其调控。这种相互作用依赖于Alu RNA中的5'假结结构域,该结构域被认为是由U-turn基序内的典型核苷酸三联体结合在一起的。在此,我们发现在U-turn基序中的一个关键鸟苷在其假结结构域中突变后,BC200的表达显著降低。我们研究了最近发现的一种短的人类Alu RNA EB120,它缺乏典型的Alu RNA U-turn核苷酸三联体。我们在18种不同的人类细胞系和组织中检测了EB120的表达。在细胞背景下,EB120被发现与SRP9/SRP14缺乏关联。小角度x射线散射和原子计算结构预测表明,BC200的Alu结构域及其U-turn突变体都具有典型的Alu RNA折叠,而EB120则没有。我们的研究结果强调了Alu RNA的结构多样性,以及突变可能对Alu RNA功能的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Alu RNA pseudoknot alterations influence SRP9/SRP14 association.

There are over 1 million Alu elements in the human genome which can be transcribed into discrete, RNA polymerase III transcribed noncoding Alu RNAs. These Alu RNAs often interact with and are regulated by the protein heterodimer SRP9/SRP14. This interaction is dependent on a 5' pseudoknot domain in the Alu RNA that is thought to be held together by a canonical nucleotide triad within a U-turn motif. Herein, we discover a significant reduction in BC200 expression after mutation of a critical guanosine in the U-turn motif within its pseudoknot domain. We studied a recently discovered short human Alu RNA, EB120, which lacks the canonical Alu RNA U-turn nucleotide triad. We tested the expression of EB120 in 18 different human cell lines and tissues. EB120 was found to lack association with SRP9/SRP14 in a cellular context. Small-angle X-ray scattering followed by atomistic computation structure prediction suggests the BC200 Alu domain and its U-turn mutant both possess a canonical Alu RNA fold, while EB120 lacks one. Our results highlight the structural diversity of Alu RNA, and the impact mutations may have on Alu RNA function.

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来源期刊
RNA
RNA 生物-生化与分子生物学
CiteScore
8.30
自引率
2.20%
发文量
101
审稿时长
2.6 months
期刊介绍: RNA is a monthly journal which provides rapid publication of significant original research in all areas of RNA structure and function in eukaryotic, prokaryotic, and viral systems. It covers a broad range of subjects in RNA research, including: structural analysis by biochemical or biophysical means; mRNA structure, function and biogenesis; alternative processing: cis-acting elements and trans-acting factors; ribosome structure and function; translational control; RNA catalysis; tRNA structure, function, biogenesis and identity; RNA editing; rRNA structure, function and biogenesis; RNA transport and localization; regulatory RNAs; large and small RNP structure, function and biogenesis; viral RNA metabolism; RNA stability and turnover; in vitro evolution; and RNA chemistry.
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