罗格斯大学Megerditch Kiledjian团队的最新研究报道了细胞外外体RNA是糖修饰的。相关论文于2025年6月4日发表在《自然—细胞生物学》杂志上。

在这里，研究团队报告了在哺乳动物细胞中使用N-叠氮乙基半乳糖胺四酰化生物正交探针进行代谢标记，揭示了小的、非编码的、糖修饰的RNAs(glycoRNAs)，这些glycoRNAs由于对glycoRNAs酶的抗性而表现出不同寻常的稳定性。这些glycoRNAs主要作为腔内货物存在于外泌体囊泡中，与最近报道的细胞表面glycoRNAs不同。重要的是，外泌体glycoRNAs可以转移到初始细胞中，突出了细胞间RNA通信的作用。外泌体生物发生的抑制导致细胞内糖核糖核酸的积累，而阻断聚糖向蛋白质的转移可减少糖核糖核酸向外泌体的分选。这些发现表明外泌体货物选择中蛋白质和RNA糖基化之间存在调节联系。他们的研究支持糖基化在靶向RNA进入外泌体中的功能作用，并揭示了基于外泌体的诊断和RNA治疗应用的潜在途径。

研究人员表示，外转录组修饰在调节RNA的稳定性、定位和功能方面起着关键作用。最近，糖基化也作为一种RNA修饰出现，尽管其功能意义尚不清楚。

附：英文原文

Title: Extracellular exosomal RNAs are glyco-modified

Author: Sharma, Sunny, Jiao, Xinfu, Yang, Jun, Kwan, Kelvin Y., Kiledjian, Megerditch

Issue&Volume: 2025-06-04

Abstract: Epitranscriptomic modifications play pivotal roles in regulating RNA stability, localization and function. Recently, glycosylation has also emerged as an RNA modification, though its functional implications remain unclear. Here we report that metabolic labelling with a N-azidoacetylgalactosamine-tetraacylated bioorthogonal probe in mammalian cells reveals small, non-coding, glyco-modified RNAs (glycoRNAs) that exhibit unusual stability imparted by their resistance to RNases. These glycoRNAs are primarily found within exosome vesicles as intraluminal cargo, distinct from recently reported cell surface glycoRNAs. Importantly, exosomal glycoRNAs can be transferred to naive cells, highlighting a role in intercellular RNA communication. The inhibition of exosome biogenesis leads to intracellular glycoRNA accumulation, while blocking glycan transfer to proteins reduces glycoRNA sorting into exosomes. These findings suggest a regulatory link between protein and RNA glycosylation in exosome cargo selection. Our studies support a functional role for glycosylation in targeting RNA into exosomes and uncover potential avenues for exosome-based diagnostics and RNA therapeutic applications.

DOI: 10.1038/s41556-025-01682-1

Source: https://www.nature.com/articles/s41556-025-01682-1