RNA-binding protein hnRNP D modulates internal ribosome entry site-dependent translation of hepatitis C virus RNA.
Hepatitis C virus (HCV) is one of the major causative agents of virus-related hepatitis, liver cirrhosis, and hepatocellular carcinoma in humans. Translation of the HCV polyprotein is mediated by an internal ribosomal entry site (IRES) in the 5' nontranslated region of the genome. Here, we report that a cellular protein, hnRNP D, interacts with the 5' border of HCV IRES (stem-loop II) and promotes translation of HCV mRNA. Overexpression of hnRNP D in mammalian cells enhances HCV IRES-dependent translation, whereas knockdown of hnRNP D with small interfering RNAs (siRNAs) inhibits translation. In addition, sequestration of hnRNP D with an interacting DNA oligomer inhibits the translation of HCV mRNA in an in vitro system. Ribosome profiling experiments reveal that HCV RNA is redistributed from heavy to light polysome fractions upon suppression of the hnRNP D level using specific siRNA. These results collectively suggest that hnRNP D plays an important role in the translation of HCV mRNA through interactions with the IRES. Moreover, knockdown of hnRNP D with siRNA significantly hampers infection by HCV. A potential role of hnRNP D in HCV proliferation is discussed.
Paek
Ki Young
KY
POSTECH Biotech Center, Department of Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea.
Kim
Chon Saeng
CS
Park
Sung Mi
SM
Kim
Jong Heon
JH
Jang
Sung Key
SK
D002460:Cell Line; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D014779:Virus Replication
D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012367:RNA, Viral