Enterovirus-induced miR-141 contributes to shutoff of host protein translation by targeting the translation initiation factor eIF4E.
Viruses rely on the host translation machinery to complete their life cycles. Picornaviruses use an internal ribosome entry site to initiate cap-independent protein translation and in parallel host cap-dependent translation is shut off. This process is thought to occur primarily via cleavage of host translation initiation factors eIF4GI and eIF4GII by viral proteases. Here we describe another mechanism whereby miR-141 induced upon enterovirus infection targets the cap-dependent translation initiation factor, eIF4E, for shutoff of host protein synthesis. Knockdown of miR-141 reduces viral propagation, and silencing of eIF4E can completely reverse the inhibitory effect of the miR-141 antagomiR on viral propagation. Ectopic expression of miR-141 promotes the switch from cap-dependent to cap-independent translation. Moreover, we identified a transcription factor, EGR1, which is partly responsible for miR-141 induction in response to enterovirus infection. Our results suggest that upregulation of miR-141 upon enterovirus infection can facilitate viral propagation by expediting the translational switch.
Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
Bing-Ching
BC
Ho
Sung-Liang
SL
Yu
Jeremy J W
JJ
Chen
Sui-Yuan
SY
Chang
Bo-Shiun
BS
Yan
Qi-Sheng
QS
Hong
Sher
S
Singh
Chuan-Liang
CL
Kao
Hsuan-Yu
HY
Chen
Kang-Yi
KY
Su
Ker-Chau
KC
Li
Chiou-Ling
CL
Cheng
Hao-Wei
HW
Cheng
Jen-Yi
JY
Lee
Chun-Nan
CN
Lee
Pan-Chyr
PC
Yang
D002460:Cell Line; D004770:Enterovirus / Q000472:pathogenicity*; D039561:Eukaryotic Initiation Factor-4E / Q000037:antagonists & inhibitors*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D008954:Models, Biological; D014176:Protein Biosynthesis
D039561:Eukaryotic Initiation Factor-4E; C533895:MIRN141 microRNA, human; D035683:MicroRNAs