Nontemplated Nucleotide Additions Distinguish the Small RNA Composition in Cells from Exosomes
Nontemplated Nucleotide Additions Distinguish the Small RNA Composition in Cells from Exosomes
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DOI：
10.1016/j.celrep.2014.08.027
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发表时间：
2014-09-25
期刊：
影响因子：
8.8
通讯作者：
Pegtel, D. Michiel
中科院分区：
文献类型：
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作者：
Koppers-Lalic, Danijela;Hackenberg, Michael;Pegtel, D. Michiel
功能生物分子，包括小的非编码RNA(NcRNAs)，通过胞外小泡(EV)在哺乳动物细胞之间释放和传递，包括内小体衍生的外切体。细胞中的小RNA组成与外体不同，但潜在的机制尚未建立。我们通过RNA测序(RNA-seq)从一组人类B细胞及其分泌的外切体中生成了小RNA图谱。综合生物信息学和统计分析揭示了微小RNA(MiRNA)物种亚群在B细胞和外切体之间的非随机分布。出乎意料的是，3‘端腺苷酸化的miRNAs在细胞中相对丰富，而3’端尿酸化的异构体在外体中似乎过度表达，这在从人类尿液样本分离的自然发生的EVS中得到了验证。综上所述，我们的发现表明，转录后修饰，特别是3‘端腺化和尿苷化，发挥相反的作用，可能至少部分地有助于引导ncRNA分选到EVS中。
Functional biomolecules, including small noncoding RNAs (ncRNAs), are released and transmitted between mammalian cells via extracellular vesicles (EVs), including endosome-derived exosomes. The small RNA composition in cells differs from exosomes, but underlying mechanisms have not been established. We generated small RNA profiles by RNA sequencing (RNA-seq) from a panel of human B cells and their secreted exosomes. A comprehensive bioinformatics and statistical analysis revealed nonrandomly distributed subsets of microRNA (miRNA) species between B cells and exosomes. Unexpectedly, 3' end adenylated miRNAs are relatively enriched in cells, whereas 3' end uridylated isoforms appear overrepresented in exosomes, as validated in naturally occurring EVs isolated from human urine samples. Collectively, our findings suggest that posttranscriptional modifications, notably 3' end adenylation and uridylation, exert opposing effects that may contribute, at least in part, to direct ncRNA sorting into EVs.