title: Cellular microRNA let-7c inhibits M1 protein expression of the H1N1 influenza A virus in infected human lung epithelial cells.
abstract: The influenza virus (IV) triggers a series of signalling events inside host cells and induces complex cellular responses. Studies have suggested that host factors play an essential role in IV replication. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that target mRNAs, triggering either translation repression or RNA degradation. Emerging research suggests that host-derived cellular miRNAs are involved in mediating the host-IV interaction. Using miRNA microarrays, we identified several miRNAs aberrantly expressed in IV-infected human lung epithelial cells (A549). Specifically, miR-let-7c was highly up-regulated in IV-infected A549 cells. PITA and miRanda database screening indicated that the let-7c seed sequence is a perfect complementary sequence match to the 3' untranslated region (UTR) of viral gene M1 (+) cRNA, but not to PB2 and PA. As detected by a luciferase reporter system, let-7c directly targeted the 3'-UTR of M1 (+) cRNA, but not PB2 and PA. To experimentally identify the function of cellular let-7c, precursor let-7c was transfected into A549 cells. Let-7c down-regulated IV M1 expression at both the (+) cRNA and protein levels. Furthermore, transfection with a let-7c inhibitor enhanced the expression of M1. Therefore, let-7c may reduce IV replication by degrading M1 (+) cRNA. This is the first report indicating that cellular miRNA regulates IV replication through the degradation of viral gene (+) cRNA by matching the 3'-UTR of the viral cRNA. These findings suggest that let-7c plays a role in protecting host cells from the virus in addition to its known cellular functions.
authors.affiliation: Lab of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Ma
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Xing-Liang
authors.initials: XL
authors.lastname: Fan
authors.forename: Hai-Bao
authors.initials: HB
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Zhen-Peng
authors.initials: ZP
authors.lastname: Li
authors.forename: Guang-Chuang
authors.initials: GC
authors.lastname: Yu
authors.forename: Xiao-Ran
authors.initials: XR
authors.lastname: Ding
authors.forename: Jun-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Bo
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Zheng
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhou
authors.forename: Sheng-Qi
authors.initials: SQ
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D019295:Computational Biology; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity* / Q000502:physiology; D007251:Influenza, Human / Q000235:genetics / Q000821:virology*; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D012333:RNA, Messenger; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D020413:3' Untranslated Regions; C488936:M1 protein, Influenza A virus; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014763:Viral Matrix Proteins; C487931:mirnlet7 microRNA, human