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In order to characterize sequence elements in the HCV 5\u2032-untranslated region (5\u2032UTR) that are possibly involved in the regulation of minus-strand RNA synthesis starting at the genome\u2019s 3\u2032end, we used a replicon system in which a possible function of these sequences is uncoupled from other functions like translation regulation. For the specific detection by RT-qPCR of minus strands newly synthesized in the cells from the transfected replicon RNAs, we carefully eliminated the contaminating DNA and transfected RNA and avoided self-priming caused by hairpin formation. We found that the absence of any HCV sequences at the 5\u2032end does not allow genome replication. Stem-loop I-II sequences only allow extremely low-level replication, whereas the presence of stem-loops I-III or the complete 5\u2032UTR allows efficient replication. The mutation of sequences required for the binding of translation initiation factor 3 (eIF3) and the ribosomal 40S subunit in the 5\u2032UTR of the plus strand severely impairs minus-strand synthesis. This suggests that eIF3 and the 40S subunit are involved in plus-strand 5\u2032-3\u2032-end communication and the regulation of minus-strand synthesis.<\/jats:p>","DOI":"10.3390\/ijms27073234","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T14:09:54Z","timestamp":1775138994000},"page":"3234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatitis C Virus 5\u2032UTR Sequences That Bind eIF3 and Ribosomal 40S Subunits Confer Stimulation of Minus-Strand RNA Synthesis"],"prefix":"10.3390","volume":"27","author":[{"given":"Attiya Qadoos","family":"Malik","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4393-1281","authenticated-orcid":false,"given":"Lyudmila","family":"Shalamova","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, 35392 Giessen, Germany"},{"name":"Institute for Virology, Faculty of Veterinary Medicine, Justus-Liebig-University, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mozhdeh","family":"Khajouei","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Budnik","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, 35392 Giessen, Germany"},{"name":"Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Giessen, Justus-Liebig-University, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lena","family":"Hell","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, 35392 Giessen, Germany"},{"name":"Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Jost","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, 35392 Giessen, Germany"},{"name":"University Children\u2019s Hospital, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gesche K.","family":"Gerresheim","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, 35392 Giessen, Germany"},{"name":"Institute for Virology, Philipps-University Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-0359","authenticated-orcid":false,"given":"Oliver","family":"Rossbach","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Faculty of Biology and Chemistry, Justus-Liebig-University, Heinrich-Buff-Ring 17, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0846-8658","authenticated-orcid":false,"given":"Michael","family":"Niepmann","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1126\/science.2523562","article-title":"Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome","volume":"244","author":"Choo","year":"1989","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1261\/rna.049338.114","article-title":"Conserved RNA secondary structures and long-range interactions in hepatitis C viruses","volume":"21","author":"Fricke","year":"2015","journal-title":"RNA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1126\/science.285.5424.110","article-title":"Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line","volume":"285","author":"Lohmann","year":"1999","journal-title":"Science"},{"key":"ref_4","first-page":"167","article-title":"Hepatitis C Virus RNA Replication","volume":"Volume 369","author":"Lohmann","year":"2013","journal-title":"Hepatitis C Virus: From Molecular Virology to Antiviral Therapy; Current Topics in Microbiology and Immunology"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Niepmann, M., Shalamova, L.A., Gerresheim, G.K., and Rossbach, O. (2018). Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00395"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"a037093","DOI":"10.1101\/cshperspect.a037093","article-title":"Hepatitis C Virus Replication","volume":"10","author":"Tabata","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Romero-L\u00f3pez, C., and Berzal-Herranz, A. (2020). The Role of the RNA-RNA Interactome in the Hepatitis C Virus Life Cycle. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041479"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/s41586-023-06301-3","article-title":"Hepatitis C virus RNA is 5\u2032-capped with flavin adenine dinucleotide","volume":"619","author":"Sherwood","year":"2023","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1128\/jvi.66.3.1476-1483.1992","article-title":"Internal ribosome entry site within hepatitis C virus RNA","volume":"66","author":"Iizuka","year":"1992","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Niepmann, M., and Gerresheim, G.K. (2020). Hepatitis C Virus Translation Regulation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072328"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1073\/pnas.96.5.2291","article-title":"In vivo analysis of the 3\u2032 untranslated region of the hepatitis C virus after in vitro mutagenesis of an infectious cDNA clone","volume":"96","author":"Yanagi","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12047","DOI":"10.1128\/JVI.75.24.12047-12057.2001","article-title":"Sequences in the 5\u2032 nontranslated region of hepatitis C virus required for RNA replication","volume":"75","author":"Friebe","year":"2001","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5326","DOI":"10.1128\/JVI.76.11.5326-5338.2002","article-title":"Genetic analysis of sequences in the 3\u2032 nontranslated region of hepatitis C virus that are important for RNA replication","volume":"76","author":"Friebe","year":"2002","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1006\/bbrc.2001.6167","article-title":"Domains I and II in the 5\u2032 nontranslated region of the HCV genome are required for RNA replication","volume":"290","author":"Kim","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9008","DOI":"10.1128\/JVI.02326-07","article-title":"A hepatitis C virus cis-acting replication element forms a long-range RNA-RNA interaction with upstream RNA sequences in NS5B","volume":"82","author":"Diviney","year":"2008","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11989","DOI":"10.1128\/JVI.01508-09","article-title":"Role of RNA structures in genome terminal sequences of the hepatitis C virus for replication and assembly","volume":"83","author":"Friebe","year":"2009","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3692","DOI":"10.1073\/pnas.1416266112","article-title":"Functionally conserved architecture of hepatitis C virus RNA genomes","volume":"112","author":"Mauger","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.molcel.2016.01.024","article-title":"The Coding Region of the HCV Genome Contains a Network of Regulatory RNA Structures","volume":"62","author":"Pirakitikulr","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8058","DOI":"10.1128\/JVI.76.16.8058-8068.2002","article-title":"Secondary structure of the 3\u2032 terminus of hepatitis C virus minus-strand RNA","volume":"76","author":"Schuster","year":"2002","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9563","DOI":"10.1128\/JVI.76.19.9563-9574.2002","article-title":"Secondary structure and hybridization accessibility of hepatitis C virus 3\u2032-terminal sequences","volume":"76","author":"Smith","year":"2002","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1111\/j.1742-4658.2005.04804.x","article-title":"Template requirements and binding of hepatitis C virus NS5B polymerase during in vitro RNA synthesis from the 3\u2032-end of virus minus-strand RNA","volume":"272","author":"Bellecave","year":"2005","journal-title":"FEBS J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12197","DOI":"10.1021\/bi800348g","article-title":"Structural domains of the 3\u2032-terminal sequence of the hepatitis C virus replicative strand","volume":"47","author":"Dutkiewicz","year":"2008","journal-title":"Biochemistry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1099\/vir.0.83067-0","article-title":"Seven nucleotide changes characteristic of the hepatitis C virus genotype 3 5\u2032 untranslated region: Correlation with reduced in vitro replication","volume":"89","author":"Masante","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.1093\/nar\/gkq109","article-title":"Identification of a structural element of the hepatitis C virus minus strand RNA involved in the initiation of RNA synthesis","volume":"38","author":"Mahias","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1006\/bbrc.1995.2526","article-title":"A novel sequence found at the 3\u2032 terminus of hepatitis C virus genome","volume":"215","author":"Tanaka","year":"1995","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1128\/jvi.70.6.3363-3371.1996","article-title":"Identification of a highly conserved sequence element at the 3\u2032 terminus of hepatitis C virus genome RNA","volume":"70","author":"Kolykhalov","year":"1996","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1093\/nar\/gkh579","article-title":"The hepatitis C virus Core protein is a potent nucleic acid chaperone that directs dimerization of the viral (+) strand RNA in vitro","volume":"32","author":"Cristofari","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1128\/JVI.78.3.1352-1366.2004","article-title":"A cis-acting replication element in the sequence encoding the NS5B RNA-dependent RNA polymerase is required for hepatitis C virus RNA replication","volume":"78","author":"You","year":"2004","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10865","DOI":"10.1128\/JVI.78.20.10865-10877.2004","article-title":"cis-acting RNA signals in the NS5B C-terminal coding sequence of the hepatitis C virus genome","volume":"78","author":"Lee","year":"2004","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1261\/rna.1680809","article-title":"A long-range RNA-RNA interaction between the 5\u2032 and 3\u2032 ends of the HCV genome","volume":"15","year":"2009","journal-title":"RNA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1093\/nar\/gkt841","article-title":"End-to-end crosstalk within the hepatitis C virus genome mediates the conformational switch of the 3\u2032X-tail region","volume":"42","author":"Briones","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1128\/JVI.79.1.380-392.2005","article-title":"Kissing-loop interaction in the 3\u2032 end of the hepatitis C virus genome essential for RNA replication","volume":"79","author":"Friebe","year":"2005","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1128\/JVI.01796-07","article-title":"3\u2032 RNA elements in hepatitis C virus replication: Kissing partners and long poly(U)","volume":"82","author":"You","year":"2008","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7044","DOI":"10.1128\/JVI.73.8.7044-7049.1999","article-title":"Specific interaction between the hepatitis C virus NS5B RNA polymerase and the 3\u2032 end of the viral RNA","volume":"73","author":"Cheng","year":"1999","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9134","DOI":"10.1128\/JVI.74.19.9134-9143.2000","article-title":"Template\/primer requirements and single nucleotide incorporation by hepatitis C virus nonstructural protein 5B polymerase","volume":"74","author":"Zhong","year":"2000","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1128\/JVI.74.4.2017-2022.2000","article-title":"De novo initiation of RNA synthesis by hepatitis C virus nonstructural protein 5B polymerase","volume":"74","author":"Zhong","year":"2000","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"33893","DOI":"10.1074\/jbc.M803094200","article-title":"Hepatitis C virus NS5B polymerase exhibits distinct nucleotide requirements for initiation and elongation","volume":"283","author":"Ferrari","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"32906","DOI":"10.1074\/jbc.M110.151316","article-title":"Further insights into the roles of GTP and the C terminus of the hepatitis C virus polymerase in the initiation of RNA synthesis","volume":"285","author":"Harrus","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7298","DOI":"10.1038\/s41467-025-62609-w","article-title":"Structural insights into polymerase-catalyzed FAD capping of hepatitis C virus RNA","volume":"16","author":"Wang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1261\/rna.2144203","article-title":"Structure-function analysis of the 3\u2032 stem-loop of hepatitis C virus genomic RNA and its role in viral RNA replication","volume":"9","author":"Yi","year":"2003","journal-title":"RNA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5857","DOI":"10.1046\/j.0014-2956.2001.02532.x","article-title":"HCV RNA-dependent RNA polymerase replicates in vitro the 3\u2032 terminal region of the minus-strand viral RNA more efficiently than the 3\u2032 terminal region of the plus RNA","volume":"268","author":"Reigadas","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8006","DOI":"10.1038\/s41467-025-63498-9","article-title":"Hepatitis C virus NS3 helicase contributes to (\u2212) strand RNA synthesis","volume":"16","author":"Ralfs","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.virol.2005.08.003","article-title":"Inhibition of hepatitis C virus replication by pol III-directed overexpression of RNA decoys corresponding to stem-loop structures in the NS5B coding region","volume":"342","author":"Zhang","year":"2005","journal-title":"Virology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"17710","DOI":"10.1074\/jbc.M908781199","article-title":"Template requirement and initiation site selection by hepatitis C virus polymerase on a minimal viral RNA template","volume":"275","author":"Oh","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6944","DOI":"10.1128\/JVI.76.14.6944-6956.2002","article-title":"Template requirements for de novo RNA synthesis by hepatitis C virus nonstructural protein 5B polymerase on the viral X RNA","volume":"76","author":"Kim","year":"2002","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1128\/JVI.76.8.3865-3872.2002","article-title":"Oligomerization and cooperative RNA synthesis activity of hepatitis C virus RNA-dependent RNA polymerase","volume":"76","author":"Wang","year":"2002","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"38838","DOI":"10.1074\/jbc.M204657200","article-title":"Modulation of hepatitis C virus RNA-dependent RNA polymerase activity by structure-based site-directed mutagenesis","volume":"277","author":"Labonte","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.antiviral.2010.04.009","article-title":"Monitoring hepatitis C virus (HCV) RNA-dependent RNA polymerase oligomerization by a FRET-based in vitro system","volume":"87","author":"Mas","year":"2010","journal-title":"Antivir. Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Clemente-Casares, P., Lopez-Jimenez, A.J., Bellon-Echeverria, I., Encinar, J.A., Martinez-Alfaro, E., Perez-Flores, R., and Mas, A. (2011). De novo polymerase activity and oligomerization of hepatitis C virus RNA-dependent RNA-polymerases from genotypes 1 to 5. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018515"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.antiviral.2014.04.009","article-title":"Hepatitis C virus polymerase-polymerase contact interface: Significance for virus replication and antiviral design","volume":"108","author":"Sabariegos","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5923","DOI":"10.1128\/JVI.02446-09","article-title":"Regulation of de novo-initiated RNA synthesis in hepatitis C virus RNA-dependent RNA polymerase by intermolecular interactions","volume":"84","author":"Chinnaswamy","year":"2010","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Gerresheim, G.K., Hess, C.S., Shalamova, L.A., Fricke, M., Marz, M., Andreev, D.E., Shatsky, I.N., and Niepmann, M. (2020). Ribosome Pausing at Inefficient Codons at the End of the Replicase Coding Region Is Important for Hepatitis C Virus Genome Replication. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186955"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Kazakov, T., Yang, F., Ramanathan, H.N., Kohlway, A., Diamond, M.S., and Lindenbach, B.D. (2015). Hepatitis C virus RNA replication depends on specific cis- and trans-acting activities of viral nonstructural proteins. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004817"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"11579","DOI":"10.1128\/JVI.00675-06","article-title":"The hepatitis C virus RNA 3\u2032-untranslated region strongly enhances translation directed by the internal ribosome entry site","volume":"80","author":"Song","year":"2006","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"001871","DOI":"10.1099\/jgv.0.001871","article-title":"A highly discriminatory RNA strand-specific assay to facilitate analysis of the role of cis-acting elements in foot-and-mouth disease virus replication","volume":"104","author":"Dobson","year":"2023","journal-title":"J. Gen. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1093\/nar\/gkz700","article-title":"Efficient inhibition of RNA self-primed extension by addition of competing 3\u2032-capture DNA-improved RNA synthesis by T7 RNA polymerase","volume":"47","author":"Gholamalipour","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1017\/S1355838201001790","article-title":"Mechanism of ribosome recruitment by hepatitis C IRES RNA","volume":"7","author":"Kieft","year":"2001","journal-title":"RNA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1126\/science.1058409","article-title":"Hepatitis C virus IRES RNA-induced changes in the conformation of the 40s ribosomal subunit","volume":"291","author":"Spahn","year":"2001","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1016\/j.str.2005.08.008","article-title":"Structure of the hepatitis C Virus IRES bound to the human 80S ribosome: Remodeling of the HCV IRES","volume":"13","author":"Boehringer","year":"2005","journal-title":"Structure"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1093\/nar\/gkn1026","article-title":"Positioning of subdomain IIId and apical loop of domain II of the hepatitis C IRES on the human 40S ribosome","volume":"37","author":"Babaylova","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1016\/j.str.2011.08.002","article-title":"Crystal structure of the HCV IRES central domain reveals strategy for start-codon positioning","volume":"19","author":"Berry","year":"2011","journal-title":"Structure"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1128\/JVI.75.3.1348-1358.2001","article-title":"Hepatitis C virus 3\u2032X region interacts with human ribosomal proteins","volume":"75","author":"Wood","year":"2001","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7861","DOI":"10.1093\/nar\/gkt543","article-title":"Hepatitis C virus 3\u2032UTR regulates viral translation through direct interactions with the host translation machinery","volume":"41","author":"Bai","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6225","DOI":"10.1093\/nar\/gkz448","article-title":"Eukaryotic initiation factor (eIF) 3 mediates Barley Yellow Dwarf Viral mRNA 3\u2032-5\u2032 UTR interactions and 40S ribosomal subunit binding to facilitate cap-independent translation","volume":"47","author":"Bhardwaj","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"199340","DOI":"10.1016\/j.virusres.2024.199340","article-title":"Recruitment of the 40S ribosomal subunit by the West Nile virus 3\u2032 UTR promotes the cross-talk between the viral genomic ends for translation regulation","volume":"343","year":"2024","journal-title":"Virus Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4230","DOI":"10.1093\/nar\/gkt075","article-title":"Unconventional miR-122 binding stabilizes the HCV genome by forming a trimolecular RNA structure","volume":"41","author":"Mortimer","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12397","DOI":"10.1093\/nar\/gkad1000","article-title":"Binding of microRNA-122 to the hepatitis C virus 5\u2032 untranslated region modifies interactions with poly(C) binding protein 2 and the NS5B viral polymerase","volume":"51","author":"Scott","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6294","DOI":"10.1128\/JVI.03631-14","article-title":"Regulation of Hepatitis C Virus Genome Replication by Xrn1 and MicroRNA-122 Binding to Individual Sites in the 5\u2032 Untranslated Region","volume":"89","author":"Thibault","year":"2015","journal-title":"J. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1099\/jgv.0.000697","article-title":"Cooperative enhancement of translation by two adjacent microRNA-122\/Argonaute 2 complexes binding to the 5 untranslated region of Hepatitis C Virus RNA","volume":"98","author":"Gerresheim","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8203","DOI":"10.1021\/bi00421a033","article-title":"Natural mRNA is required for directing Met-tRNA(f) binding to 40S ribosomal subunits in animal cells: Involvement of Co-eIF-2A in natural mRNA-directed initiation complex formation","volume":"27","author":"Roy","year":"1988","journal-title":"Biochemistry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1038\/s41467-018-05053-3","article-title":"microRNA-122 amplifies hepatitis C virus translation by shaping the structure of the internal ribosomal entry site","volume":"9","author":"Schult","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1093\/nar\/gkad094","article-title":"Elucidating the distinct contributions of miR-122 in the HCV life cycle reveals insights into virion assembly","volume":"51","author":"Rheault","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/j.1348-0421.2000.tb02532.x","article-title":"Hepatitis C virus NS5B RNA replicase specifically binds ribosomes","volume":"44","author":"Tanaka","year":"2000","journal-title":"Microbiol. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1006\/jmbi.2000.3687","article-title":"Protein-protein interaction among hnRNPs shuttling between nucleus and cytoplasm","volume":"298","author":"Kim","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1261\/rna.7070304","article-title":"Multimerization of poly(rC) binding protein 2 is required for translation initiation mediated by a viral IRES","volume":"10","author":"Bedard","year":"2004","journal-title":"RNA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0168-1702(00)00228-8","article-title":"Interaction of poly(rC)-binding protein 2 with the 5\u2032-terminal stem loop of the hepatitis C-virus genome","volume":"73","author":"Fukushi","year":"2001","journal-title":"Virus Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"7954","DOI":"10.1128\/JVI.00339-11","article-title":"Poly(C)-binding protein 2 interacts with sequences required for viral replication in the hepatitis C virus (HCV) 5\u2032 untranslated region and directs HCV RNA replication through circularizing the viral genome","volume":"85","author":"Wang","year":"2011","journal-title":"J. Virol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.chom.2014.12.014","article-title":"miR-122 stimulates hepatitis C virus RNA synthesis by altering the balance of viral RNAs engaged in replication versus translation","volume":"17","author":"Masaki","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.bbrc.2006.06.144","article-title":"Subproteomic analysis of the cellular proteins associated with the 3\u2032 untranslated region of the hepatitis C virus genome in human liver cells","volume":"347","author":"Pan","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Cousineau, S.E., Camargo, C., and Sagan, S.M. (2024). Poly(rC)-Binding Protein 2 Does Not Directly Participate in HCV Translation or Replication, but Rather Modulates Genome Packaging. Viruses, 16.","DOI":"10.3390\/v16081220"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1126\/science.1113329","article-title":"Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA","volume":"309","author":"Jopling","year":"2005","journal-title":"Science"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1002\/j.1460-2075.1990.tb07540.x","article-title":"A short cis-acting sequence is required for hepatitis B virus pregenome encapsidation and sufficient for packaging of foreign RNA","volume":"9","author":"Bartenschlager","year":"1990","journal-title":"EMBO J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.1002\/j.1460-2075.1992.tb05420.x","article-title":"Hepadnaviral assembly is initiated by polymerase binding to the encapsidation signal in the viral RNA genome","volume":"11","author":"Bartenschlager","year":"1992","journal-title":"EMBO J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.tim.2019.04.003","article-title":"RNA Packaging in HIV","volume":"27","author":"Rein","year":"2019","journal-title":"Trends Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Shi, G., Ando, T., Suzuki, R., Matsuda, M., Nakashima, K., Ito, M., Omatsu, T., Oba, M., Ochiai, H., and Kato, T. (2016). Involvement of the 3\u2032 Untranslated Region in Encapsidation of the Hepatitis C Virus. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005441"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"22952","DOI":"10.1038\/srep22952","article-title":"Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging","volume":"6","author":"Stewart","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/nrmicro3098","article-title":"The ins and outs of hepatitis C virus entry and assembly","volume":"11","author":"Lindenbach","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_88","first-page":"725","article-title":"Firefly luciferase gene: Structure and expression in mammalian cells","volume":"7","author":"Wood","year":"1987","journal-title":"Mol. Cell. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7408","DOI":"10.1073\/pnas.0504877103","article-title":"Construction and characterization of infectious intragenotypic and intergenotypic hepatitis C virus chimeras","volume":"103","author":"Pietschmann","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"8416","DOI":"10.1128\/jvi.71.11.8416-8428.1997","article-title":"Biochemical properties of hepatitis C virus NS5B RNA-dependent RNA polymerase and identification of amino acid sequence motifs essential for enzymatic activity","volume":"71","author":"Lohmann","year":"1997","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1006\/viro.1996.0164","article-title":"Homotypic interaction and multimerization of hepatitis C virus core protein","volume":"218","author":"Matsumoto","year":"1996","journal-title":"Virology"},{"key":"ref_92","first-page":"113","article-title":"Hepatitis C virus proteins: From structure to function","volume":"Volume 369","author":"Moradpour","year":"2013","journal-title":"Hepatitis C Virus: From Molecular Virology to Antiviral Therapy; Current Topics in Microbiology and Immunology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1021\/acschembio.5b00753","article-title":"NanoLuc Complementation Reporter Optimized for Accurate Measurement of Protein Interactions in Cells","volume":"11","author":"Dixon","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e2505538122","DOI":"10.1073\/pnas.2505538122","article-title":"Structural insights into the role of eIF3 in translation mediated by the HCV IRES","volume":"122","author":"Iwasaki","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"13001","DOI":"10.1128\/JVI.76.24.13001-13014.2002","article-title":"Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication","volume":"76","author":"Blight","year":"2002","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1128\/JVI.77.1.115-122.2003","article-title":"Impaired binding of standard initiation factors mediates poliovirus translation attenuation","volume":"77","author":"Ochs","year":"2003","journal-title":"J. Virol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1128\/jvi.62.8.2636-2643.1988","article-title":"A segment of the 5\u2032 nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation","volume":"62","author":"Jang","year":"1988","journal-title":"J. Virol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1080\/15257770.2018.1533138","article-title":"The effects of pH and salts on nucleic acid partitioning during phenol extraction","volume":"38","author":"Xu","year":"2019","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_99","first-page":"49","article-title":"Probing the Heterogeneity of Ionic Liquids in Solution through Phenol-Water Phase Behavior","volume":"4","author":"Verma","year":"2019","journal-title":"Electro Phys. Theor. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Bernhart, S.H., Hofacker, I.L., Will, S., Gruber, A.R., and Stadler, P.F. (2008). RNAalifold: Improved consensus structure prediction for RNA alignments. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-474"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1093\/bioinformatics\/btp250","article-title":"VARNA: Interactive drawing and editing of the RNA secondary structure","volume":"25","author":"Darty","year":"2009","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3234\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T04:33:50Z","timestamp":1775277230000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,2]]},"references-count":101,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27073234"],"URL":"https:\/\/doi.org\/10.3390\/ijms27073234","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,2]]}}}