小柯机器人

美国哈佛医学院C. Ronald Kahn小组的最新研究发现MicroRNA序列介导细胞外囊泡释放和细胞滞留。该项研究成果发表在2021年12月22日出版的《自然》上。

研究人员发现miRNA具有确定其在细胞外小囊泡 (sEV)（EXOmotifs）或细胞滞留（CELLmotifs）的分泌序列，并且在不同的细胞类型，包括白色和棕色脂肪细胞、内皮细胞、肝脏和肌肉，优先使用特定的分泌序列，因此具有细胞类型特异性sEV miRNA谱。在miRNA中插入或删除这些CELL motifs 或 EXO motifs会增加或减少细胞中产生或分泌到外泌体/sEVs的miRNA。

两种RNA结合蛋白Alyref和Fus参与具有最强EXO motif（CGGGAG） miRNA的输出。 EXO motifs介导的miRNA传递增加会造成对远处细胞中靶基因的抑制作用增强。因此，该miRNA序列不仅提供了人们对循环外泌体miRNA来源组织的理解，还提供了一种改进RNA介导靶向治疗的思路。

研究人员表示，外泌体和其他sEV提供了一种独特的细胞间通讯模式，其中从一个细胞产生和释放的microRNA (miRNA)可以传递到远处的细胞，从而改变基因表达。然而，对于miRNAs如何分配到外泌体/sEVs或保留在细胞中的机制仍然未知。

附：英文原文

Title: MicroRNA sequence codes for small extracellular vesicle release and cellular retention

Author: Garcia-Martin, Ruben, Wang, Guoxiao, Brando, Bruna B., Zanotto, Tamires M., Shah, Samah, Kumar Patel, Sandip, Schilling, Birgit, Kahn, C. Ronald

Issue&Volume: 2021-12-22

Abstract: Exosomes and other small extracellular vesicles (sEVs) provide a unique mode of cell-to-cell communication in which microRNAs (miRNAs) produced and released from one cell are taken up by cells at a distance where they can enact changes in gene expression1,2,3. However, the mechanism by which miRNAs are sorted into exosomes/sEVs or retained in cells remains largely unknown. Here we demonstrate that miRNAs possess sorting sequences that determine their secretion in sEVs (EXOmotifs) or cellular retention (CELLmotifs) and that different cell types, including white and brown adipocytes, endothelium, liver and muscle, make preferential use of specific sorting sequences, thus defining the sEV miRNA profile of that cell type. Insertion or deletion of these CELLmotifs or EXOmotifs in a miRNA increases or decreases retention in the cell of production or secretion into exosomes/sEVs. Two RNA-binding proteins, Alyref and Fus, are involved in the export of miRNAs carrying one of the strongest EXOmotifs, CGGGAG. Increased miRNA delivery mediated by EXOmotifs leads to enhanced inhibition of target genes in distant cells. Thus, this miRNA code not only provides important insights that link circulating exosomal miRNAs to tissues of origin, but also provides an approach for improved targeting in RNA-mediated therapies.

DOI: 10.1038/s41586-021-04234-3

Source: https://www.nature.com/articles/s41586-021-04234-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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