PDF(Pubmed)
Abstract：
Non-coding RNAs (ncRNAs) are important regulators of gene expression. They are expressed not only in cells, but also in cell-derived extracellular vesicles (EVs). The mechanisms controlling their loading and sorting remain poorly understood. Here, we investigated the impact of TP53 mutations on the non-coding RNA content of small melanoma EVs. After purification of small EVs from six different patient-derived melanoma cell lines, we characterized them by small RNA sequencing and lncRNA microarray analysis. We found that TP53 mutations are associated with a specific micro and long non-coding RNA content in small EVs. Then, we showed that long and small non-coding RNAs enriched in TP53 mutant small EVs share a common sequence motif, highly similar to the RNA-binding motif of Sam68, a protein interacting with hnRNP proteins. This protein thus may be an interesting partner of p53, involved in the expression and loading of the ncRNAs. To conclude, our data support the existence of cellular mechanisms associate with TP53 mutations which control the ncRNA content of small EVs in melanoma.
摘要：
非编码RNA(ncRNAs)是基因表达的重要调控因子。它们不仅在细胞中表达，而且在细胞来源的细胞外囊泡（EV）。控制它们的装载和分选的机制仍然知之甚少。这里,我们调查了TP53突变对小黑色素瘤EVs非编码RNA含量的影响.在从六种不同的患者来源的黑色素瘤细胞系中纯化小电动汽车后，我们通过小RNA测序和lncRNA微阵列分析对它们进行了表征。我们发现TP53突变与小型电动汽车中特定的微小和长非编码RNA含量有关。然后，我们表明，富含TP53突变小EV的长和小的非编码RNA共享一个共同的序列基序，与与hnRNP蛋白相互作用的蛋白质Sam68的RNA结合基序高度相似。因此，该蛋白质可能是p53的有趣伴侣，参与ncRNA的表达和加载。最后，我们的数据支持存在与TP53突变相关的细胞机制,TP53突变控制黑色素瘤中小型EV的ncRNA含量.
