Exomeres and Supermeres: monolithic or diverse?
Exomeres and Supermeres: monolithic or diverse?
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外粒细胞和超粒细胞：整体还是多样化？
DOI：
10.1002/jex2.45
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Witwer,Kenneth
中科院分区：
文献类型：
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作者：
Tosar,JuanPablo;Cayota,Alfonso;Witwer,Kenneth
细胞外囊泡（EVs），包括外泌体和微囊泡，远不是唯一含有RNA的细胞外颗粒（EPs）。最近，通过不对称流场分离发现了新的35纳米大小的EPs，并将其称为“外显子”。外显子的纯化后来也通过差示超离心进行。最近，用于收集外显子的高速超离心的上清被进一步离心，以收集一种新的EP，称为“超级粒”。超粒含有大量的细胞外RNA，并在miR‐1246中富集。它们还富含疾病生物标志物，可以诱导受体细胞的代谢和适应性变化。在这里，我们重新分析了在这项令人兴奋的研究中获得的蛋白质组学和转录组学数据，以进一步了解外显子和超显子的分子组成。我们发现超粒中排名靠前的rna对应于细胞外蛋白复合物的足迹。这些复合物保护小核RNA U2和28S rRNA片段免受细胞外核糖核酸酶（exRNases）的攻击。我们认为，细胞内的纳米颗粒，如U2核糖核蛋白、核糖体和LGALS3BP环状十体被释放到细胞外空间。这些异质EPs可能会被外显子酶进一步处理，并与外显子和超显子的其他组分进行超离心共分离。我们期待在定义exRNA载体方面继续取得进展，将过程定义与分子组成和功能联系起来。
Extracellular vesicles (EVs), including exosomes and microvesicles, are far from being the only RNA‐containing extracellular particles (EPs). Recently, new 35‐nm‐sized EPs were discovered by asymmetric‐flow field‐flow fractionation and termed ‘exomeres’. Purification of exomeres was later performed by differential ultracentrifugation as well. More recently, the supernatant of the high‐speed ultracentrifugation used to collect exomeres was further centrifuged to collect a new class of EP, termed ‘supermeres’. Supermeres contain high quantities of extracellular RNA and are enriched in miR‐1246. They are also replete in disease biomarkers and can induce metabolic and adaptive changes in recipient cells. Here, we reanalysed proteomic and transcriptomic data obtained in this exciting study to obtain further insights into the molecular composition of exomeres and supermeres. We found that the top‐ranking RNAs in supermeres correspond to the footprints of extracellular protein complexes. These complexes protect fragments of the small nuclear RNA U2 and the 28S rRNA from extracellular ribonucleases (exRNases). We suggest that intracellular nanoparticles such as the U2 ribonucleoprotein, ribosomes and LGALS3BP ring‐like decamers are released into the extracellular space. These heterogeneous EPs might be further processed by exRNases and co‐isolate by ultracentrifugation with other components of exomeres and supermeres. We look forward to continuing progress in defining exRNA carriers, bridging process definitions with molecular composition and function.