The Hepatitis C virus internal ribosome entry site, or HCVIRES, is an RNA structure within the 5'UTR of the HCV genome that mediates cap-independent translation initiation.
Protein translation of most eukaryoticmRNAs occurs by a cap-dependent mechanism and requires association of Met-tRNAiMet, several eukaryotic initiation factors, and GTP with the 40S ribosomal subunit, recruitment to the 5' cap, and scanning along the 5' UTR to reach to start codon. In contrast, translation of hepatitis C virus (HCV) mRNA is initiated by a different mechanism from the usual 5' cap-binding model.[1] This alternate mechanism relies on the direct binding of the 40S ribosomal subunit by the internal ribosome entry site (IRES) in the 5' UTR of HCV RNA. The HCV IRES adopts a complex structure, and may differ significantly from IRES elements identified in picornaviruses. A small number of eukaryotic mRNA have been shown to be translated by internal ribosome entry.[2][3]
Nucleotides 1–40 of the HCV mRNA are thought not to contribute to translation, and are rather required for genomicRNA replication. The remainder of the HCV 5'-UTR consists of three domains, namely domains II-IV (domain I is located on the 5'-end of the mRNA).[citation needed]
Mechanism of actionEdit
HCV IRES independently binds two components of eukaryotic translation initiation machinery, the multiprotein initiation factor eIF3 and 40S small ribosomal subunit. Moreover, it binds 40S in such a manner that AUG initiator codon is positioned in the ribosomal P-site, thus no ribosomal scanning is required. Consequently scanning factors eIF1 and eIF1A are dispensable for the HCV translation, as are components of the eIF4F complex (eIF4A, eIF4E, and eIF4G) and eIF4B, which are generally required for mRNA binding and unwinding of 5'UTR. Initiator tRNA is delivered either by eIF2 or, in stress conditions when eIF2 is inactivated, by eIF2A, eIF2D, or possibly eIF5B, a homologue of prokaryotic IF2 protein.[citation needed]
^Lytle JR, Wu L, Robertson HD (August 2002). "Domains on the hepatitis C virus internal ribosome entry site for 40s subunit binding". RNA. 8 (8): 1045–1055. doi:10.1017/S1355838202029965. PMC1370315. PMID 12212848.
^Beales LP, Rowlands DJ, Holzenburg A (May 2001). "The internal ribosome entry site (IRES) of hepatitis C virus visualized by electron microscopy". RNA. 7 (5): 661–670. doi:10.1017/S1355838201001406. PMC1370118. PMID 11350030.
^Gallego J, Varani G (April 2002). "The hepatitis C virus internal ribosome-entry site: a new target for antiviral research". Biochemical Society Transactions. 30 (2): 140–145. doi:10.1042/BST0300140. PMID 12023841.
Further readingEdit
Malygin AA, Kossinova OA, Shatsky IN, Karpova GG (October 2013). "HCV IRES interacts with the 18S rRNA to activate the 40S ribosome for subsequent steps of translation initiation". Nucleic Acids Research. 41 (18): 8706–8714. doi:10.1093/nar/gkt632. PMC3794592. PMID 23873958.
External linksEdit
Page for Hepatitis C virus internal ribosome entry site at Rfam
October 19, 2023
hepatitis, virus, internal, ribosome, entry, site, ires, structure, within, genome, that, mediates, independent, translation, initiation, predicted, secondary, structure, sequence, conservation, ires, hcvidentifierssymbolires, hcvalt, symbolshcv, iresrfamrf000. The Hepatitis C virus internal ribosome entry site or HCV IRES is an RNA structure within the 5 UTR of the HCV genome that mediates cap independent translation initiation Hepatitis C virus internal ribosome entry sitePredicted secondary structure and sequence conservation of IRES HCVIdentifiersSymbolIRES HCVAlt SymbolsHCV IRESRfamRF00061Other dataRNA typeCis reg IRESDomain s VirusesGOGO 0043022SOSO 0000243PDB structuresPDBeProtein translation of most eukaryotic mRNAs occurs by a cap dependent mechanism and requires association of Met tRNAiMet several eukaryotic initiation factors and GTP with the 40S ribosomal subunit recruitment to the 5 cap and scanning along the 5 UTR to reach to start codon In contrast translation of hepatitis C virus HCV mRNA is initiated by a different mechanism from the usual 5 cap binding model 1 This alternate mechanism relies on the direct binding of the 40S ribosomal subunit by the internal ribosome entry site IRES in the 5 UTR of HCV RNA The HCV IRES adopts a complex structure and may differ significantly from IRES elements identified in picornaviruses A small number of eukaryotic mRNA have been shown to be translated by internal ribosome entry 2 3 Contents 1 IRES structure 2 Mechanism of action 3 See also 4 References 5 Further reading 6 External linksIRES structure EditNucleotides 1 40 of the HCV mRNA are thought not to contribute to translation and are rather required for genomic RNA replication The remainder of the HCV 5 UTR consists of three domains namely domains II IV domain I is located on the 5 end of the mRNA citation needed Mechanism of action EditHCV IRES independently binds two components of eukaryotic translation initiation machinery the multiprotein initiation factor eIF3 and 40S small ribosomal subunit Moreover it binds 40S in such a manner that AUG initiator codon is positioned in the ribosomal P site thus no ribosomal scanning is required Consequently scanning factors eIF1 and eIF1A are dispensable for the HCV translation as are components of the eIF4F complex eIF4A eIF4E and eIF4G and eIF4B which are generally required for mRNA binding and unwinding of 5 UTR Initiator tRNA is delivered either by eIF2 or in stress conditions when eIF2 is inactivated by eIF2A eIF2D or possibly eIF5B a homologue of prokaryotic IF2 protein citation needed See also EditEukaryotic translation Eukaryotic initiation factorReferences Edit Lytle JR Wu L Robertson HD August 2002 Domains on the hepatitis C virus internal ribosome entry site for 40s subunit binding RNA 8 8 1045 1055 doi 10 1017 S1355838202029965 PMC 1370315 PMID 12212848 Beales LP Rowlands DJ Holzenburg A May 2001 The internal ribosome entry site IRES of hepatitis C virus visualized by electron microscopy RNA 7 5 661 670 doi 10 1017 S1355838201001406 PMC 1370118 PMID 11350030 Gallego J Varani G April 2002 The hepatitis C virus internal ribosome entry site a new target for antiviral research Biochemical Society Transactions 30 2 140 145 doi 10 1042 BST0300140 PMID 12023841 Further reading EditMalygin AA Kossinova OA Shatsky IN Karpova GG October 2013 HCV IRES interacts with the 18S rRNA to activate the 40S ribosome for subsequent steps of translation initiation Nucleic Acids Research 41 18 8706 8714 doi 10 1093 nar gkt632 PMC 3794592 PMID 23873958 External links EditPage for Hepatitis C virus internal ribosome entry site at Rfam Retrieved from https en wikipedia org w index php title Hepatitis C virus internal ribosome entry site amp oldid 1117284218, wikipedia, wiki, book, books, library,
