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

Ho et al. Cell  9, 58-69( 2011)

Speaker: Chia-Ming Chang (張家銘)                            Time:15:10 ~ 16:00, May. 4, 2011

Commentator: Dr. Shu-ying Wang (王淑鶯老師)        Place: Room 601

Abstract:

Virus relys on the host to complete its protein translation and replication cycle. It is well known that enterovirus 71, the RNA virus of the family picornaviridae shutoff host translation machinery by cleavage translation initiation factor eIF4GI and eIF4GII by viral protease 2A [1]. In this paper, the authors provide a new mechanism that virus infection results in host translation shutoff and induces a protein translation switch from cap-dependent to a cap-independent form[2], which helps viral protein synthesis and replication. Host protein translation shutoff activity was associated with microRNA-141 and its target gene, the translation initiation factor eIF4E, which plays a important role in cap-denpendent translation, microRNA is non-coding, small RNA,  binding with 3’-untranslated region of target mRNA by seed region and function on degrading target mRNA or repressing translation by interfere ribosome binding to mRNA. In the first, the authors found microRNA-141 was upregualted after EV71 infection by real-time PCR, and the miR-141 repressed eIF4E expression and resulted in translation switch in in vitro study and the antagomir-141 reversed eIF4E expression and attenuated virulence by inhibition virus replication and viral protein synthesis. The authors also revealed that miR-141 expression is partly regulated by transcription factor EGR1 by truncated regulated element promoter assay and siRNA experiment. All together, this paper provides a new insight into research the association between virus , microRNA and host, and the antagomir may be a new candidate of antiviral molecular.

References:

1.     Gradi, A et al.(1998). Proteolysis of human eukaryotic translation initiation       factor eIF4GII, but not eIF4GI, coincides with the shutoff of host protein synthesis after poliovirus infection. Proc. Natl.Acad. Sci. USA 95, 11089–11094.

2.     Lin, J.Y. el al.(2009). Viral and host proteins involved in picornavirus life cycle.        J. Biomed.Sci. 16, 103.