胶质母细胞瘤是人类最致命的脑部疾病之一。尽管最近的研究表明，N6-甲基腺苷（m6A）修饰与长非编码RNA（lncRNA）在胶质瘤发生和恶性进展中存在相互作用，但胶质母细胞瘤中m6A介导的lncRNA翻译调节机制仍不清楚。在此，我们对胶质瘤干细胞和分化胶质瘤细胞的转录组、翻译组和表观转录组进行了分析，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 表现出翻译效率降低。转录本水平表达分析表明 m6A 在可翻译 lncRNA 转录本的短开放阅读框 (sORF) 周围富集。对不同RNA区域m6A修饰的进一步比较分析表明，sORF下游的m6A峰比上游的m6A峰更能抑制lncRNA翻译。对神经胶质瘤相关 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。总体而言，这些发现阐明了 m6A 甲基化组的动态特征，并增强了对 lncRNA 翻译调控复杂性的理解。© 作者 2024。由牛津大学出版社出版。版权所有。如需权限，请发送电子邮件至：journals.permissions@oup.com。

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.© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.