Multi-omics integration analysis reveals the role of N6-methyladenosine in lncRNA translation during glioma stem cell differentiation.

IF 2.5 3区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Briefings in Functional Genomics Pub Date : 2024-12-06 DOI:10.1093/bfgp/elae037

Meng Zhang, Runqiu Cai, Jingjing Liu, Yulan Wang, Shan He, Quan Wang, Xiaofeng Song, Jing Wu, Jian Zhao

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Abstract

Glioblastoma is one of the most lethal brain diseases in humans. Although recent studies have shown reciprocal interactions between N6-methyladenosine (m6A) modifications and long noncoding RNAs (lncRNAs) in gliomagenesis and malignant progression, the mechanism of m6A-mediated lncRNA translational regulation in glioblastoma remains unclear. Herein, we profiled the transcriptomes, translatomes, and epitranscriptomics of glioma stem cells and differentiated glioma cells to investigate the role of m6A in lncRNA translation comprehensively. We found that lncRNAs with numerous m6A peaks exhibit reduced translation efficiency. Transcript-level expression analysis demonstrates an enrichment of m6A around short open reading frames (sORFs) of translatable lncRNA transcripts. Further comparison analysis of m6A modifications in different RNA regions indicates that m6A peaks downstream of sORFs inhibit lncRNA translation more than those upstream. Observations in glioma-associated lncRNAs H19, LINC00467, and GAS5 further confirm the negative effect of m6A methylation on lncRNA translation. Overall, these findings elucidate the dynamic profiles of the m6A methylome and enhance the understanding of the complexity of lncRNA translational regulation.

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多组学整合分析揭示 N6-甲基腺苷在胶质瘤干细胞分化过程中 lncRNA 翻译中的作用

胶质母细胞瘤是人类致死率最高的脑部疾病之一。尽管最近的研究表明，N6-甲基腺苷（m6A）修饰和长非编码 RNA（lncRNA）在胶质瘤的发生和恶性进展中存在相互作用，但 m6A 介导的 lncRNA 在胶质母细胞瘤中的翻译调控机制仍不清楚。在此，我们分析了胶质瘤干细胞和分化胶质瘤细胞的转录组、翻译组和表转录组，以全面研究m6A在lncRNA翻译中的作用。我们发现，具有大量 m6A 峰的 lncRNA 翻译效率降低。转录本水平的表达分析表明，在可翻译的 lncRNA 转录本的短开放阅读框（sORF）周围富集了 m6A。对不同 RNA 区域的 m6A 修饰的进一步比较分析表明，sORFs 下游的 m6A 峰比上游的 m6A 峰更能抑制 lncRNA 的翻译。对胶质瘤相关 lncRNA H19、LINC00467 和 GAS5 的观察进一步证实了 m6A 甲基化对 lncRNA 翻译的负面影响。总之，这些发现阐明了 m6A 甲基化组的动态轮廓，加深了人们对 lncRNA 翻译调控复杂性的理解。

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

Briefings in Functional Genomics BIOTECHNOLOGY & APPLIED MICROBIOLOGY-GENETICS & HEREDITY

CiteScore

6.30

自引率

2.50%

发文量

审稿时长

6-12 weeks

期刊介绍： Briefings in Functional Genomics publishes high quality peer reviewed articles that focus on the use, development or exploitation of genomic approaches, and their application to all areas of biological research. As well as exploring thematic areas where these techniques and protocols are being used, articles review the impact that these approaches have had, or are likely to have, on their field. Subjects covered by the Journal include but are not restricted to: the identification and functional characterisation of coding and non-coding features in genomes, microarray technologies, gene expression profiling, next generation sequencing, pharmacogenomics, phenomics, SNP technologies, transgenic systems, mutation screens and genotyping. Articles range in scope and depth from the introductory level to specific details of protocols and analyses, encompassing bacterial, fungal, plant, animal and human data. The editorial board welcome the submission of review articles for publication. Essential criteria for the publication of papers is that they do not contain primary data, and that they are high quality, clearly written review articles which provide a balanced, highly informative and up to date perspective to researchers in the field of functional genomics.