Hepatitis C Virus Translation Regulation
Translation of the hepatitis C virus (HCV) RNA genome is regulated by the internal ribosome entry site (IRES), located in the 5’-untranslated region (5′UTR) and part of the core protein coding sequence, and by the 3′UTR. The 5′UTR has some highly conserved structural regions, while others can assume...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/7/2328 |
| _version_ | 1797626567671676928 |
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| author | Michael Niepmann Gesche K. Gerresheim |
| author_facet | Michael Niepmann Gesche K. Gerresheim |
| author_sort | Michael Niepmann |
| collection | DOAJ |
| description | Translation of the hepatitis C virus (HCV) RNA genome is regulated by the internal ribosome entry site (IRES), located in the 5’-untranslated region (5′UTR) and part of the core protein coding sequence, and by the 3′UTR. The 5′UTR has some highly conserved structural regions, while others can assume different conformations. The IRES can bind to the ribosomal 40S subunit with high affinity without any other factors. Nevertheless, IRES activity is modulated by additional <i>cis</i> sequences in the viral genome, including the 3′UTR and the <i>cis</i>-acting replication element (CRE). Canonical translation initiation factors (eIFs) are involved in HCV translation initiation, including eIF3, eIF2, eIF1A, eIF5, and eIF5B. Alternatively, under stress conditions and limited eIF2-Met-tRNA<sub>i</sub><sup>Met</sup> availability, alternative initiation factors such as eIF2D, eIF2A, and eIF5B can substitute for eIF2 to allow HCV translation even when cellular mRNA translation is downregulated. In addition, several IRES trans-acting factors (ITAFs) modulate IRES activity by building large networks of RNA-protein and protein–protein interactions, also connecting 5′- and 3′-ends of the viral RNA. Moreover, some ITAFs can act as RNA chaperones that help to position the viral AUG start codon in the ribosomal 40S subunit entry channel. Finally, the liver-specific microRNA-122 (miR-122) stimulates HCV IRES-dependent translation, most likely by stabilizing a certain structure of the IRES that is required for initiation. |
| first_indexed | 2024-03-11T10:12:17Z |
| format | Article |
| id | doaj.art-de346dff7d874de9a7acb8243fa47bed |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T10:12:17Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-de346dff7d874de9a7acb8243fa47bed2023-11-16T14:29:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-03-01217232810.3390/ijms21072328Hepatitis C Virus Translation RegulationMichael Niepmann0Gesche K. Gerresheim1Institute of Biochemistry, Medical Faculty, Justus-Liebig-University, Friedrichstrasse 24, 35392 Giessen, GermanyInstitute of Biochemistry, Medical Faculty, Justus-Liebig-University, Friedrichstrasse 24, 35392 Giessen, GermanyTranslation of the hepatitis C virus (HCV) RNA genome is regulated by the internal ribosome entry site (IRES), located in the 5’-untranslated region (5′UTR) and part of the core protein coding sequence, and by the 3′UTR. The 5′UTR has some highly conserved structural regions, while others can assume different conformations. The IRES can bind to the ribosomal 40S subunit with high affinity without any other factors. Nevertheless, IRES activity is modulated by additional <i>cis</i> sequences in the viral genome, including the 3′UTR and the <i>cis</i>-acting replication element (CRE). Canonical translation initiation factors (eIFs) are involved in HCV translation initiation, including eIF3, eIF2, eIF1A, eIF5, and eIF5B. Alternatively, under stress conditions and limited eIF2-Met-tRNA<sub>i</sub><sup>Met</sup> availability, alternative initiation factors such as eIF2D, eIF2A, and eIF5B can substitute for eIF2 to allow HCV translation even when cellular mRNA translation is downregulated. In addition, several IRES trans-acting factors (ITAFs) modulate IRES activity by building large networks of RNA-protein and protein–protein interactions, also connecting 5′- and 3′-ends of the viral RNA. Moreover, some ITAFs can act as RNA chaperones that help to position the viral AUG start codon in the ribosomal 40S subunit entry channel. Finally, the liver-specific microRNA-122 (miR-122) stimulates HCV IRES-dependent translation, most likely by stabilizing a certain structure of the IRES that is required for initiation.https://www.mdpi.com/1422-0067/21/7/2328HCV<i>Hepacivirus</i>internal ribosome entry siteIRESinitiationribosome |
| spellingShingle | Michael Niepmann Gesche K. Gerresheim Hepatitis C Virus Translation Regulation International Journal of Molecular Sciences HCV <i>Hepacivirus</i> internal ribosome entry site IRES initiation ribosome |
| title | Hepatitis C Virus Translation Regulation |
| title_full | Hepatitis C Virus Translation Regulation |
| title_fullStr | Hepatitis C Virus Translation Regulation |
| title_full_unstemmed | Hepatitis C Virus Translation Regulation |
| title_short | Hepatitis C Virus Translation Regulation |
| title_sort | hepatitis c virus translation regulation |
| topic | HCV <i>Hepacivirus</i> internal ribosome entry site IRES initiation ribosome |
| url | https://www.mdpi.com/1422-0067/21/7/2328 |
| work_keys_str_mv | AT michaelniepmann hepatitiscvirustranslationregulation AT geschekgerresheim hepatitiscvirustranslationregulation |