Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation
Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation
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DOI：
10.1016/j.celrep.2018.11.073
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发表时间：
2018-12-18
期刊：
影响因子：
8.8
通讯作者：
Ansel, K. Mark
中科院分区：
文献类型：
--
作者：
Chiou, Ni-Ting;Kageyama, Robin;Ansel, K. Mark
microRNA （miRNA）在细胞外囊泡（ev）中分选的发现揭示了一种新的细胞间通讯模式，并揭示了细胞内膜区室与ev分泌细胞中小rna之间的联系。使用两步超离心程序分离T细胞释放的ev，我们发现与相应的细胞RNA相比，ev中45%的tRNA片段（trf）和不到1%的mirna显著富集。T细胞激活诱导ev介导的一组特定trf的释放，这些trf来自trna的5‘端和3’内区域，没有可变环。抑制EV生物发生途径特异性地导致这些激活诱导的EV富集tRFs在多泡体（MVBs）中积累。引入反义寡核苷酸抑制这些trf可增强T细胞的活化。综上所述，这些结果表明T细胞通过MVBs选择性地将tRFs释放到ev中，这一过程可能会去除抑制免疫激活的tRFs。
The discovery of microRNA ( miRNA) sorting into extracellular vesicles (EVs) revealed a novel mode of intercellular communication and uncovered a link between cellular endomembrane compartments and small RNAs in EV-secreting cells. Using a two-step ultracentrifugation procedure to isolate EVs released by T cells, we found that 45% of tRNA fragments (tRFs), but fewer than 1% of miRNAs, were significantly enriched in EVs compared with the corresponding cellular RNA. T cell activation induced the EV-mediated release of a specific set of tRFs derived from the 5' end and 3'-internal region of tRNAs without variable loops. Inhibition of EV biogenesis pathways specifically led to the accumulation of these activation-induced EV-enriched tRFs within multivesicular bodies (MVBs). Introducing antisense oligonucleotides to inhibit these tRFs enhanced T cell activation. Taken together, these results demonstrate that T cells selectively release tRFs into EVs via MVBs and suggest that this process may remove tRFs that repress immune activation.