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World J Gastroenterol. Aug 14, 2018; 24(30): 3374-3383
Published online Aug 14, 2018. doi: 10.3748/wjg.v24.i30.3374
Form confers function: Case of the 3’X region of the hepatitis C virus genome
Mariola Dutkiewicz, Jerzy Ciesiołka
Mariola Dutkiewicz, Jerzy Ciesiołka, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan 61-704, Poland
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Supported by the Polish Ministry of Science and Higher Education under the KNOW program and Foundation for Polish Science, No. POMOST/2013-8/5.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mariola Dutkiewicz, PhD, Associate Professor, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, Poznan 61-704, Poland. mariolad@ibch.poznan.pl
Telephone: +48-61-8528503 Fax: +48-61-8528532
Received: April 28, 2018
Peer-review started: April 28, 2018
First decision: June 11, 2018
Revised: June 25, 2018
Accepted: June 30, 2018
Article in press: June 30, 2018
Published online: August 14, 2018
Abstract

At the 3’ end of genomic hepatitis C virus (HCV) RNA there is a highly conserved untranslated region, the 3’X-tail, which forms part of the 3’UTR. This region plays key functions in regulation of critical processes of the viral life cycle. The 3’X region is essential for viral replication and infectivity. It is also responsible for regulation of switching between translation and transcription of the viral RNA. There is some evidence indicating the contribution of the 3’X region to the translation efficiency of the viral polyprotein and to the encapsidation process. Several different secondary structure models of the 3’X region, based on computer predictions and experimental structure probing, have been proposed. It is likely that the 3’X region adopts more than one structural form in infected cells and that a specific equilibrium between the various forms regulates several aspects of the viral life cycle. The most intriguing explanations of the structural heterogeneity problem of the 3’X region came with the discovery of its involvement in long-range RNA-RNA interactions and the potential for homodimer formation. This article summarizes current knowledge on the structure and function of the 3’X region of hepatitis C genomic RNA, reviews previous opinions, presents new hypotheses and summarizes the questions that still remain unanswered.

Keywords: Hepatitis C virus, 3’UTR, 3’X-tail, 3’X region, 3’X RNA, RNA structure

Core tip: Several different secondary structure models of the 3’X region have been proposed. It is likely that the 3’X region adopts more than one structural form in infected cells and that a specific equilibrium between the various forms regulates several aspects of the viral life cycle. This article summarizes current knowledge of the structure and function of the 3’X region of hepatitis C genomic RNA, reviews previous opinions, presents new hypotheses and summarizes the questions that still remain unanswered.