Enterovirus-induced miR-141 contributes to shutoff of host protein translation by targeting the translation initiation factor elF4E (Cell Host & Microbe, 2011, 9:58-69)

報告日期: 2011/03/15
報告時間: 16:00/16:50
報告學生: 王莉萩
講評老師: 劉校生
附件下載:

Full text: http://basicmed.med.ncku.edu.tw/admin/up_img/000315-2.pdf

Enterovirus-induced miR-141 contributes to shutoff of host protein translation by targeting the translation initiation factor eIF4E
Bing-Chin Ho, et al. (2011) Cell Host & Microbe 9:58-69.

Speaker: Li-Chiu Wang
Commentator: Dr. Hsiao-Sheng Liu
Place: Room 602
Time: 2011/3/17 16:10-17:00

Enteroviruses with positive single stranded RNA genomes belong to family Picornaviridae. They are known to induce a large amount of modifications on host translation machinery causing shutoff of cap-dependent host protein synthesis and re-directing the machinery to favor viral protein productions. This phenomenon is called translation switch. Furthermore, the genomes of enteroviruses carry internal ribosome entry site (IRES) elements to initiate viral protein translation independent of cap-structure (1). Previous studies show that canonical initiation factors, eIF2, eIF3, eIF4A and eIF4G are involved in IRES-dependent protein translation (2). The roles of eIF4E in translation switch, however, remains controversial. In the present study, the authors demonstrated that eIF4E expression was suppressed as early as 2 hours post-infection in enterovirus-infected cells. Down-regulation of eIF4E was resulted from the elevated expression of miR-141 which targeted to the 3’-UTR of eIF4E mRNA. In addition, suppression of eIF4E expression led to translation switch that favors viral replications. AntagomiR-141, an antagonist of miR-141, not only restored the expression of eIF4E, attenuated the translation switch, but also reduced the viral replication in infected cells. The phenomenon was also observed in enterovirus-infected neural cells, which are the major target cells for polio virus and enterovirus 71, the causative agents of fatal poliomyelitis and encephalitis. The authors further identified early growth response 1 mediated, at least partially, the induction of miR-141 in infected cells. In conclusion, the authors clarified that suppression of eIF4E expression by miR-141 triggers translation switch. In addition, enterovirus infections regulate miR-141 expression through early growth response 1. These findings might be used as new therapeutic targets for fatal enterovirus infections.

References
1. Biochemica et Biophysica Acta (2009) 1789:542-557.
2. Journal of General Virology (2008) 89:611-626.