1] Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain [2] Servicio de Inmunología, Hospital de la Princesa, Madrid 28006, Spain.
Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain.
Nat Commun. 2013;4:2980. doi: 10.1038/ncomms3980.
Exosomes are released by most cells to the extracellular environment and are involved in cell-to-cell communication. Exosomes contain specific repertoires of mRNAs, microRNAs (miRNAs) and other non-coding RNAs that can be functionally transferred to recipient cells. However, the mechanisms that control the specific loading of RNA species into exosomes remain unknown. Here we describe sequence motifs present in miRNAs that control their localization into exosomes. The protein heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) specifically binds exosomal miRNAs through the recognition of these motifs and controls their loading into exosomes. Moreover, hnRNPA2B1 in exosomes is sumoylated, and sumoylation controls the binding of hnRNPA2B1 to miRNAs. The loading of miRNAs into exosomes can be modulated by mutagenesis of the identified motifs or changes in hnRNPA2B1 expression levels. These findings identify hnRNPA2B1 as a key player in miRNA sorting into exosomes and provide potential tools for the packaging of selected regulatory RNAs into exosomes and their use in biomedical applications.
外泌体由大多数细胞释放到细胞外环境中，并参与细胞间通讯。外泌体包含特定的 mRNA、microRNAs（miRNAs）和其他非编码 RNA 谱，这些 RNA 谱可以被功能性地转移到受体细胞中。然而，控制 RNA 物种特异性装载到外泌体中的机制尚不清楚。在这里，我们描述了控制 miRNA 定位到外泌体的 miRNA 中存在的序列基序。蛋白质异质核核糖核蛋白 A2B1（hnRNPA2B1）通过识别这些基序特异性地结合外泌体 miRNA，并控制其装载到外泌体中。此外，外泌体中的 hnRNPA2B1 被 SUMO 化，SUMO 化控制 hnRNPA2B1 与 miRNA 的结合。通过对鉴定的基序进行突变或改变 hnRNPA2B1 的表达水平，可以调节 miRNA 装载到外泌体中。这些发现确定了 hnRNPA2B1 在外泌体中 miRNA 分选中的关键作用，并为将选定的调节 RNA 包装到外泌体中并将其用于生物医学应用提供了潜在的工具。
