Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells.
Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells.
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DOI：
10.1093/nar/gks832
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发表时间：
2012-11
影响因子：
14.9
通讯作者：
Hill AF
中科院分区：
文献类型：
--
作者：
Bellingham SA;Coleman BM;Hill AF
朊病毒病是影响人类和动物的传染性神经退行性疾病。细胞朊病毒蛋白 PrPC 和异常感染形式 PrPSc 被发现与外泌体相关，外泌体是从细胞中释放的 50-130 nm 的小囊泡。外泌体还含有 microRNA (miRNA)，一类非编码 RNA，已被用来识别 miRNA 特征以诊断疾病。虽然一些 miRNA 在感染朊病毒的脑组织中失调，但 miRNA 在朊病毒疾病期间释放的循环外泌体中的作用尚不清楚。在这里，我们研究了从感染朊病毒的神经元细胞释放的外泌体中的 miRNA 谱。我们对外泌体进行了首次小RNA深度测序研究，证明神经元外泌体含有多种RNA种类，包括逆转录病毒RNA重复区、信使RNA片段、转移RNA片段、非编码RNA、小核RNA、小核仁RNA、小细胞质RNA、沉默RNA以及已知和新型候选miRNA。值得注意的是，我们发现与未感染的外泌体相比，受朊病毒感染的神经元细胞释放的外泌体增加了let-7b、let-7i、miR-128a、miR-21、miR-222、miR-29b、miR-342-3p和miR-424的水平，同时降低了miR-146a的水平。总体而言，这些结果表明，朊病毒感染期间释放的循环外泌体具有独特的 miRNA 特征，可用于诊断和了解朊病毒疾病的致病机制。
Prion diseases are transmissible neurodegenerative disorders affecting both humans and animals. The cellular prion protein, PrPC, and the abnormal infectious form, PrPSc, are found associated with exosomes, which are small 50–130 nm vesicles released from cells. Exosomes also contain microRNAs (miRNAs), a class of non-coding RNA, and have been utilized to identify miRNA signatures for diagnosis of disease. While some miRNAs are deregulated in prion-infected brain tissue, the role of miRNA in circulating exosomes released during prion disease is unknown. Here, we investigated the miRNA profile in exosomes released from prion-infected neuronal cells. We performed the first small RNA deep sequencing study of exosomes and demonstrated that neuronal exosomes contain a diverse range of RNA species including retroviral RNA repeat regions, messenger RNA fragments, transfer RNA fragments, non-coding RNA, small nuclear RNA, small nucleolar RNA, small cytoplasmic RNA, silencing RNA as well as known and novel candidate miRNA. Significantly, we show that exosomes released by prion-infected neuronal cells have increased let-7b, let-7i, miR-128a, miR-21, miR-222, miR-29b, miR-342-3p and miR-424 levels with decreased miR-146 a levels compared to non-infected exosomes. Overall, these results demonstrate that circulating exosomes released during prion infection have a distinct miRNA signature that can be utilized for diagnosis and understanding pathogenic mechanisms in prion disease.
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影响因子：
2.5
作者：
Li YY;Cui JG;Hill JM;Bhattacharjee S;Zhao Y;Lukiw WJ
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DOI：
10.1073/pnas.0308413101
发表时间：
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影响因子：
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作者：
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