Precursor miR-886, a novel noncoding RNA repressed in cancer, associates with PKR and modulates its activity |
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Authors: | Lee Kwanbok Kunkeaw Nawapol Jeon Sung Ho Lee Inhan Johnson Betty H Kang Gum-Yong Bang Joo Young Park Hyung Soon Leelayuwat Chanvit Lee Yong Sun |
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Institution: | Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA. |
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Abstract: | 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, eIF2α phosphorylation and the NF-κB 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. |
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Keywords: | cancer microRNA noncoding RNA PKR vault RNA |
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