Differential stimulation of hepatitis C virus RNA translation by microRNA-122 in different cell cycle phases
Volume 11, Issue 2
Downloads and Tools
January 15, 2012
Pages 277 - 285http://dx.doi.org/10.4161/cc.11.2.18699
Authors: Carmen Fehr, K. Dominik Conrad and Michael Niepmann View affiliations
Hepatitis C virus (HCV) replicates preferentially in the liver, and in most cases the HCV infection becomes chronic and often results in hepatocellular carcinoma. When the HCV plus-strand RNA genome has been delivered to the cytosol of the infected cell, its translation is directed by the Internal Ribosome Entry Site (IRES) in the 5´-untranslated region (5´-UTR) of the viral RNA. Thereby, IRES activity is modulated by several host factors. In particular, the liver-specific microRNA-122 (miR-122) interacts with two target sites in the HCV 5´-UTR and stimulates HCV translation, thereby most likely contributing to HCV liver tropism. Here we show that HCV IRES-dependent translation efficiency in the hepatoma cell line Huh7 is highest during the G0 and G1 phases of the cell cycle but significantly drops during the S phase and even more in the G2/M phase. The superimposed stimulation of HCV translation by ectopic miR-122 works best during the G0, G1 and G2/M phases but is lower during the S phase. However, the levels of Ago2 protein do not substantially change during cell cycle phases, indicating that other cellular factors involved in HCV translation stimulation by miR-122 may be differentially expressed in different cell cycle phases. Moreover, the levels of endogenously expressed miR-122 in Huh7 cells are lowest in the S phase, indicating that the predominant G0/G1 state of non-dividing hepatocytes in the liver facilitates high expression of the HCV genome and stimulation by miR-122, with yet unknown factors involved in the differential extent of stimulation by miR-122.
Received: May 20, 2011; Accepted: November 7, 2011