title: Precursor miR-886, a novel noncoding RNA repressed in cancer, associates with PKR and modulates its activity.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
authors.forename: Kwanbok
authors.initials: K
authors.lastname: Lee
authors.forename: Nawapol
authors.initials: N
authors.lastname: Kunkeaw
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Jeon
authors.forename: Inhan
authors.initials: I
authors.lastname: Lee
authors.forename: Betty H
authors.initials: BH
authors.lastname: Johnson
authors.forename: Gum-Yong
authors.initials: GY
authors.lastname: Kang
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Bang
authors.forename: Hyung Soon
authors.initials: HS
authors.lastname: Park
authors.forename: Chanvit
authors.initials: C
authors.lastname: Leelayuwat
authors.forename: Yong Sun
authors.initials: YS
authors.lastname: Lee
mesh_terms: D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D012322:RNA Precursors / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: C559060:MIRN886 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012322:RNA Precursors; D012330:RNA, Double-Stranded; D019892:eIF-2 Kinase