N6-甲基腺苷(m6A)是真核生物中最丰富的转录后动态RNA修饰过程,广泛参与细胞生长,胚胎发育和免疫稳态。m6A最深刻的生物学功能之一是调节RNA代谢,从而决定了RNA的命运。值得注意的是,m6A介导的有组织的RNA代谢的调节关键依赖于无膜细胞器(MLO)在细胞核和细胞质中的组装,比如核斑点,应力颗粒和加工体。此外,m6A相关的MLO在控制包括转录在内的各种RNA代谢过程中发挥关键作用,拼接,运输,衰减和翻译。然而,新出现的证据表明,m6A水平失调有助于在一系列人类疾病中形成病理性凝聚物,包括肿瘤发生,生殖疾病,神经系统疾病和呼吸系统疾病。迄今为止,m6A调节与RNA代谢相关的生物分子缩合物聚集的分子机制尚不清楚.在这次审查中,我们全面总结了与M6A相关的MLO的最新生化过程,特别关注它们对RNA代谢的影响以及它们在疾病发展和相关生物学机制中的关键作用。此外,我们认为,m6A相关的MLO可作为疾病进展的预测标志物和未来潜在的药物靶点.
N6-methyladenosine (m6A) is the most abundant post-transcriptional dynamic RNA modification process in eukaryotes, extensively implicated in cellular growth, embryonic development and immune homeostasis. One of the most profound biological functions of m6A is to regulate RNA metabolism, thereby determining the fate of RNA. Notably, the regulation of m6A-mediated organized RNA metabolism critically relies on the assembly of membraneless organelles (MLOs) in both the nucleus and
cytoplasm, such as nuclear speckles, stress granules and processing bodies. In addition, m6A-associated MLOs exert a pivotal role in governing diverse RNA metabolic processes encompassing transcription, splicing, transport, decay and translation. However, emerging evidence suggests that dysregulated m6A levels contribute to the formation of pathological condensates in a range of human diseases, including tumorigenesis, reproductive diseases, neurological diseases and respiratory diseases. To date, the molecular mechanism by which m6A regulates the aggregation of biomolecular condensates associated with RNA metabolism is unclear. In this review, we comprehensively summarize the updated biochemical processes of m6A-associated MLOs, particularly focusing on their impact on RNA metabolism and their pivotal role in disease development and related biological mechanisms. Furthermore, we propose that m6A-associated MLOs could serve as predictive markers for disease progression and potential drug targets in the future.