tetano
Editor, Senior Moderator
J Cell Mol Med. 2012 Mar 27. doi: 10.1111/j.1582-4934.2012.01572.x. [Epub ahead of print]
Cellular MicroRNA let-7c Inhibits M1 Protein Expression of the H1N1 Influenza A Virus in Infected Human Lung Epithelial Cells.
Ma YJ, Yang J, Fan XL, Zhao HB, Hu W, Li ZP, Yu GC, Ding XR, Wang JZ, Bo XC, Zheng XF, Zhou Z, Wang SQ.
Source
Lab of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, 100850, P. R, China; Astronaut Research and Training Center of China, Beijing, 100094, P.R, China.
Abstract
The influenza virus (IV) triggers a series of signaling 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 upregulated 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 downregulated 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.
? 2012 The Authors Journal of Cellular and Molecular Medicine ? 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
PMID:
22452878
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22452878
Cellular MicroRNA let-7c Inhibits M1 Protein Expression of the H1N1 Influenza A Virus in Infected Human Lung Epithelial Cells.
Ma YJ, Yang J, Fan XL, Zhao HB, Hu W, Li ZP, Yu GC, Ding XR, Wang JZ, Bo XC, Zheng XF, Zhou Z, Wang SQ.
Source
Lab of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, 100850, P. R, China; Astronaut Research and Training Center of China, Beijing, 100094, P.R, China.
Abstract
The influenza virus (IV) triggers a series of signaling 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 upregulated 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 downregulated 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.
? 2012 The Authors Journal of Cellular and Molecular Medicine ? 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
PMID:
22452878
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22452878