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

Autor: Zhang M; Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 29 Jiangjun Avenue, Jiangning District, Nanjing 211106, Jiangsu Province, China., Cai R; Equipment Department, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Qinhuai District, Nanjing 210029, Jiangsu Province, China., Liu J; Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 29 Jiangjun Avenue, Jiangning District, Nanjing 211106, Jiangsu Province, China., Wang Y; Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 29 Jiangjun Avenue, Jiangning District, Nanjing 211106, Jiangsu Province, China., He S; Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 29 Jiangjun Avenue, Jiangning District, Nanjing 211106, Jiangsu Province, China., Wang Q; Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 29 Jiangjun Avenue, Jiangning District, Nanjing 211106, Jiangsu Province, China., Song X; Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 29 Jiangjun Avenue, Jiangning District, Nanjing 211106, Jiangsu Province, China., Wu J; School of Biomedical Engineering and Informatics, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing 211166, Jiangsu Province, China., Zhao J; Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, No. 29 Jiangjun Avenue, Jiangning District, Nanjing 211106, Jiangsu Province, China.
Jazyk: angličtina
Zdroj: Briefings in functional genomics [Brief Funct Genomics] 2024 Dec 06; Vol. 23 (6), pp. 806-815.
DOI: 10.1093/bfgp/elae037
Abstrakt: 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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Databáze: MEDLINE