Recurrent chimeric fusion RNAs in non-cancer tissues and cells.
Recurrent chimeric fusion RNAs in non-cancer tissues and cells.
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DOI：
10.1093/nar/gkw032
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发表时间：
2016-04-07
影响因子：
14.9
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Babiceanu M;Qin F;Xie Z;Jia Y;Lopez K;Janus N;Facemire L;Kumar S;Pang Y;Qi Y;Lazar IM;Li H
基因融合及其产物（RNA和蛋白质）曾被认为是癌症的独特特征。然而，嵌合RNA也可以在正常细胞中发现。在这里，我们执行，策划和分析了近300个RNA-Seq文库，涵盖30种不同的非肿瘤人类组织和细胞以及15种小鼠组织。结果发现大量的融合基因转录本，其中大部分融合基因只被检测到一次，而291个融合基因在多个样本中被检测到。我们专注于复发性融合，并对一个子集进行RNA和蛋白质水平验证。我们根据融合体的各种特征及其亲本基因来表征这些融合体。与非复发性基因相比，它们倾向于以相对于其亲本基因更高的水平表达。超过一半的复发性融合涉及相邻基因以相同方向转录。发现一些序列基序富集在融合连接位点附近。我们对一些广泛表达的融合体进行了功能分析，发现沉默它们会导致正常细胞生长和/或运动性的显著降低。大多数嵌合体使用典型的剪接位点，因此可能是“基因间剪接”的产物。我们还探讨了这些非病理性融合在癌症和进化中的意义。
Gene fusions and their products (RNA and protein) were once thought to be unique features to cancer. However, chimeric RNAs can also be found in normal cells. Here, we performed, curated and analyzed nearly 300 RNA-Seq libraries covering 30 different non-neoplastic human tissues and cells as well as 15 mouse tissues. A large number of fusion transcripts were found. Most fusions were detected only once, while 291 were seen in more than one sample. We focused on the recurrent fusions and performed RNA and protein level validations on a subset. We characterized these fusions based on various features of the fusions, and their parental genes. They tend to be expressed at higher levels relative to their parental genes than the non-recurrent ones. Over half of the recurrent fusions involve neighboring genes transcribing in the same direction. A few sequence motifs were found enriched close to the fusion junction sites. We performed functional analyses on a few widely expressed fusions, and found that silencing them resulted in dramatic reduction in normal cell growth and/or motility. Most chimeras use canonical splicing sites, thus are likely products of ‘intergenic splicing’. We also explored the implications of these non-pathological fusions in cancer and in evolution.