Precursor miR-886, a novel noncoding RNA repressed in cancer, associates with PKR and modulates its activity
Precursor miR-886, a novel noncoding RNA repressed in cancer, associates with PKR and modulates its activity
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DOI：
10.1261/rna.2701111
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发表时间：
2011-06-01
期刊：
影响因子：
4.5
通讯作者：
Lee, Yong Sun
中科院分区：
文献类型：
--
作者：
Lee, Kwanbok;Kunkeaw, Nawapol;Lee, Yong Sun
非编码RNA最近引起了生物学界的广泛关注。尽管目前的研究高度倾向于 microRNA，但对其他非编码 RNA 的研究却相对滞后。在这里，我们研究了一种新型非编码 RNA，称为前体 microRNA miR-886 (pre-miR-886)。 Pre-miR-886 也被提议作为穹窿 RNA，它是与癌症耐药性有关的穹窿复合体的一个组成部分。我们鉴定出 pre-miR-886 是一种 102 个核苷酸长、丰富的细胞质 RNA，它既不是真正的 pre-microRNA，也不是穹窿 RNA。 Pre-miR-886 与 PKR（RNA 激活蛋白激酶）物理相关，PKR 是一种干扰素诱导型双链 RNA 依赖性激酶。 pre-miR-886 的抑制会激活 PKR 及其下游通路、eIF2 α 磷酸化和 NF-kappa B 通路，导致细胞增殖受损。我们还发现 pre-miR-886 在多种癌细胞系和临床样本中受到抑制。这项研究是对 pre-miR-886 的首次深入表征，也是对其作为 PKR 调节剂功能的初步报告，这表明其在肿瘤发生中发挥着关键作用。
Noncoding RNAs have drawn significant attention in biology recently. Whereas the current research is highly inclined to microRNAs, research on other noncoding RNAs has lagged behind. Here, we investigated a novel noncoding RNA that has been known as precursor microRNA miR-886 (pre-miR-886). Pre-miR-886 has been proposed also as a vault RNA, a component of the vault complex implicated in cancer drug resistance. We identified pre-miR-886 as a 102-nucleotide-long, abundant cytoplasmic RNA that is neither a genuine pre-microRNA nor a vault RNA. Pre-miR-886 is physically associated with PKR (Protein Kinase RNA-activated), an interferon-inducible and double-stranded RNA dependent kinase. The suppression of pre-miR-886 activates PKR and its downstream pathways, eIF2 alpha phosphorylation and the NF-kappa B pathway, leading to impaired cell proliferation. We also found that pre-miR-886 is suppressed in a wide-range of cancer cell lines and in clinical specimens. This study is the first intense characterization of pre-miR-886 as well as the initial report on its function as a PKR regulator, which suggests a critical role in tumorigenesis.