eEF1A1 regulates the expression and alternative splicing of genes associated with Parkinson's disease in U251 cells.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-07-01 Epub Date: 2024-05-22 DOI:10.1007/s13258-024-01516-8

Jing Lei, Guliqiemu Aimaier, Zaolaguli Aisha, Yan Zhang, Jianhua Ma

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Abstract

Background: Eukaryotic elongation factor 1A1 (eEF1A1) is an RNA-binding protein that is associated with PARK2 activity in cells, suggesting a possible role in Parkinson's disease (PD).

Objective: To clear whether eEF1A1 plays a role in PD through transcriptional or posttranscriptional regulation.

Methods: The GSE68719 dataset was downloaded from the GEO database, and the RNA-seq data of all brain tissue autopsies were obtained from 29 PD patients and 44 neurologically normal control subjects. To inhibit eEF1A1 from being expressed in U251 cells, siRNA was transfected into those cells, and RNA-seq high-throughput sequencing was used to determine the differentially expressed genes (DEGs) and differentially alternative splicing events (ASEs) resulting from eEF1A1 knockdown.

Results: eEF1A1 was significantly overexpressed in PD brain tissue in the BA9 area. GO and KEGG enrichment analyses revealed that eEF1A1 knockdown significantly upregulated the expression of the genes CXCL10, NGF, PTX3, IL6, ST6GALNAC3, NUPR1, TNFRSF21, and CXCL2 and upregulated the alternative splicing of the genes ACOT7, DDX10, SHMT2, MYEF2, and NDUFAF5. These genes were enriched in pathways related to PD pathogenesis, such as apoptosis, inflammatory response, and mitochondrial dysfunction.

Conclusion: The results suggesting that eEF1A1 involved in the development of PD by regulating the differential expression and alternative splicing of genes, providing a theoretical basis for subsequent research.

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eEF1A1 在 U251 细胞中调控帕金森病相关基因的表达和替代剪接。

背景：真核细胞延伸因子1A1（eEF1A1）是一种RNA结合蛋白，在细胞中与PARK2的活性相关，提示其可能在帕金森病（PD）中发挥作用：目的：明确 eEF1A1 是通过转录调控还是转录后调控在帕金森病中发挥作用：方法：从GEO数据库下载GSE68719数据集，获得29例帕金森病患者和44例神经正常对照组所有脑组织尸检的RNA-seq数据。为了抑制eEF1A1在U251细胞中的表达，研究人员将siRNA转染到这些细胞中，并利用RNA-seq高通量测序确定了因eEF1A1被敲除而导致的差异表达基因（DEG）和差异替代剪接事件（ASE）。GO和KEGG富集分析显示，敲除eEF1A1可显著上调CXCL10、NGF、PTX3、IL6、ST6GALNAC3、NUPR1、TNFRSF21和CXCL2基因的表达，并上调ACOT7、DDX10、SHMT2、MYEF2和NDUFAF5基因的替代剪接。这些基因富集在与帕金森病发病机制相关的通路中，如细胞凋亡、炎症反应和线粒体功能障碍：结果表明，eEF1A1通过调控基因的差异表达和替代剪接参与了帕金森病的发病，为后续研究提供了理论依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.