miR-122 does not modulate the elongation phase of hepatitis C virus RNA synthesis in isolated replicase complexes.

Antiviral Research
Rodrigo A VillanuevaStanley M Lemon

Abstract

miR-122 is an abundant, liver-specific microRNA that is required for efficient amplification of hepatitis C virus (HCV) RNA. Recent studies with a miR-122-specific locked nucleic acid antagomir have shown it to be an important host target for therapeutic intervention. However, considerable controversy exists concerning the mechanisms underlying the dependence of HCV replication on miR-122. We studied the impact of miR-122 on the rate of [(32)P]-incorporation into positive-strand viral RNA by membrane-bound replicase complexes isolated from cells containing HCV RNA replicons. [(32)P]-incorporation in this cell-free system represents primarily the elongation phase of RNA synthesis, with little or no de novo initiation, and was not affected by the addition of either excess miR-122 or a miR-122-specific antisense oligonucleotide that suppresses replication in vivo. We also found no evidence that detectable quantities of miR-122 are specifically associated with replicase complexes in vivo. These results are consistent with miR-122 acting at an alternative step in the viral life cycle, promoting cap-independent viral translation, enhancing viral RNA stability, or facilitating de novo initiation of viral RNA synthesis.

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Citations

Feb 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Shihyun YouCharles M Rice
Jan 5, 2012·Proceedings of the National Academy of Sciences of the United States of America·Tetsuro ShimakamiStanley M Lemon
Dec 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·You LiStanley M Lemon
Oct 15, 2013·PloS One·Youkyung ChoiKris Krawczynski
Dec 29, 2012·International Journal of Molecular Sciences·Letizia Da Sacco, Andrea Masotti
Jul 12, 2012·Hepatitis Monthly·Hossein Sendi
Feb 6, 2014·Life Sciences·Cristian TuratoPatrizia Pontisso
Oct 26, 2013·Archives of Virology·K Dominik Conrad, Michael Niepmann
Aug 25, 2015·Biochemical and Biophysical Research Communications·Sergio HernándezRodrigo A Villanueva
Jul 25, 2013·Wiley Interdisciplinary Reviews. RNA·Joyce A Wilson, Adam Huys
Oct 14, 2014·Journal of Hepatology·Simonetta BandieraMirjam B Zeisel
Mar 30, 2012·Journal of Biomedical Science and Engineering·Jie LiuHuixiao Hong
Jan 20, 2012·RNA Biology·Catherine Jopling
Jun 19, 2013·RNA Biology·You LiStanley M Lemon
Apr 2, 2013·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Patricia A Thibault, Joyce A Wilson
Apr 24, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yogita K Adlakha, Neeru Saini
Jan 2, 2018·Virusdisease·Iqra AlmasSadia Zahid
May 31, 2016·F1000Research·Renumathy DhanasekaranLewis R Roberts
Sep 21, 2013·Physiological Genomics·Gokul SwaminathanSonia Navas-Martin
Dec 2, 2010·Biochemical Society Transactions·Andrew P Lewis, Catherine L Jopling
Mar 30, 2018·Frontiers in Microbiology·Michael NiepmannOliver Rossbach

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