Enterovirus-Induced miR-141 Contributes to Shutoff of Host Protein Translation by Targeting the Translation Initiation Factor eIF4E

Ho B-C, Yu S-L, Chen JJW, et al. Cell Host & Microbe 2011; 9: 58-69

Speaker: Pei-Wei Chen (陳珮瑋)                                  Time: 13:10~14:00, Jan. 02, 2013

Commentator: Dr. Hsiao-Sheng Liu (劉校生 老師)   Place: Room 601

Abstract:

Human enteroviruses infect millions of people worldwide each year, resulting in a wide range of clinical symptoms.⁽¹⁾ Recently, enterovirus 71 (EV71) has become a newly emerging life-threatening pathogen, especially in the Asia-Pacific region. The genome of enteroviruses is a single-stranded plus sense RNA molecule and uses internal ribosome entry site to initiate protein translation, independent of cap structure.⁽²⁾ MicroRNAs (miRNAs) are recently discovered as a class of small non-protein-coding RNAs that govern a wide range of biological functions including host-virus interaction. However, few studies have explored the role of miRNAs in virus infection, and whether miRNAs contribute to the blockage of host protein synthesis is still unknown. In this study, the authors analyzed the expression profiles of microRNAs in EV71-infected rhadomyosarcoma cells, and microRNA-141 (miR-141) was abundantly increased in EV71-infected cells. Results showed that miR-141 targeted eIF4E mRNA and mediated the suppression of eIF4E by targeting prediction programs and verifying in reporter-expression assays. eIF4E is a cap-binding protein that is involved in facilitating host cap-dependent translation and is a major target for translational control. The antagomiR-141 was used to block the induction of miR-141 in infected cells. The silencing of eIF4E was able to entirely rescue the decrease of viral propagation caused by antagomiR-141, suggesting that virus-induced miR-141 might play a major role in controlling the suppression of eIF4E and the success of viral replication. They used luciferase reporter assays to explore the regulatory mechanisms of EV71-induced miR-141 expression. Results showed that EV71-upregulated early growth response 1 could increase miR-141 expression. Consequently, miR-141 induction leads to the silencing of eIF4E and the reduction in eIF4E results in a protein synthesis switch from cap-dependent to cap-independent translation that might contribute to viral pathogenesis and virus propagation.

Reference:

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