Initiation factor-independent translation mediated by the hepatitis C virus internal ribosome entry site
The hepatitis C viral mRNA initiates translation using an internal ribosome entry site (IRES) located in the 5' noncoding region of the viral genome. At physiological magnesium ion concentrations, the HCV IRES forms a binary complex with the 40S ribosomal subunit, recruits initiation factor eIF...
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| Veröffentlicht in: | RNA (Cambridge) 2006-05, Vol.12 (5), p.894-902 |
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| creator | Lancaster, Alissa M Jan, Eric Sarnow, Peter |
| description | The hepatitis C viral mRNA initiates translation using an internal ribosome entry site (IRES) located in the 5' noncoding region of the viral genome. At physiological magnesium ion concentrations, the HCV IRES forms a binary complex with the 40S ribosomal subunit, recruits initiation factor eIF3 and the ternary eIF2/GTP/Met-tRNA(i)Met complex, and joins 60S subunits to assemble translation-competent 80S ribosomes. Here we show that in the presence of 5 mM MgCl2, the HCV IRES can initiate translation by an alternative mechanism that does not require known initiation factors. Specifically, the HCV IRES was shown to initiate translation in a reconstituted system consisting only of purified 40S and 60S subunits, elongation factors, and aminoacylated tRNAs at high magnesium concentration. Analyses of assembled complexes supported a mechanism by which preformed 80S ribosomes can assemble directly on the HCV IRES at high cation concentrations. This mechanism is reminiscent of that employed by the divergent IRES elements in the Dicistroviridae, exemplified by the cricket paralysis virus, which mediates initiation of protein synthesis without initiator tRNA. |
| doi_str_mv | 10.1261/rna.2342306 |
| format | Article |
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At physiological magnesium ion concentrations, the HCV IRES forms a binary complex with the 40S ribosomal subunit, recruits initiation factor eIF3 and the ternary eIF2/GTP/Met-tRNA(i)Met complex, and joins 60S subunits to assemble translation-competent 80S ribosomes. Here we show that in the presence of 5 mM MgCl2, the HCV IRES can initiate translation by an alternative mechanism that does not require known initiation factors. Specifically, the HCV IRES was shown to initiate translation in a reconstituted system consisting only of purified 40S and 60S subunits, elongation factors, and aminoacylated tRNAs at high magnesium concentration. Analyses of assembled complexes supported a mechanism by which preformed 80S ribosomes can assemble directly on the HCV IRES at high cation concentrations. 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At physiological magnesium ion concentrations, the HCV IRES forms a binary complex with the 40S ribosomal subunit, recruits initiation factor eIF3 and the ternary eIF2/GTP/Met-tRNA(i)Met complex, and joins 60S subunits to assemble translation-competent 80S ribosomes. Here we show that in the presence of 5 mM MgCl2, the HCV IRES can initiate translation by an alternative mechanism that does not require known initiation factors. Specifically, the HCV IRES was shown to initiate translation in a reconstituted system consisting only of purified 40S and 60S subunits, elongation factors, and aminoacylated tRNAs at high magnesium concentration. Analyses of assembled complexes supported a mechanism by which preformed 80S ribosomes can assemble directly on the HCV IRES at high cation concentrations. This mechanism is reminiscent of that employed by the divergent IRES elements in the Dicistroviridae, exemplified by the cricket paralysis virus, which mediates initiation of protein synthesis without initiator tRNA.</description><subject>Aminoacylation</subject><subject>Animals</subject><subject>Cattle</subject><subject>Centrifugation, Density Gradient</subject><subject>Codon, Initiator</subject><subject>Cricket paralysis virus</subject><subject>Dicistrovirus</subject><subject>Edeine - pharmacology</subject><subject>HeLa Cells</subject><subject>Hepacivirus - physiology</subject><subject>Hepatitis C virus</subject><subject>Humans</subject><subject>Liver - metabolism</subject><subject>Magnesium - pharmacology</subject><subject>Peptide Chain Initiation, Translational</subject><subject>Peptide Initiation Factors</subject><subject>Protein Biosynthesis</subject><subject>Ribosomes - metabolism</subject><subject>RNA, Transfer - metabolism</subject><subject>RNA, Viral - physiology</subject><subject>Transcription, Genetic</subject><issn>1355-8382</issn><issn>1469-9001</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtLAzEUhYMotlZX7iUrNzKax0wy2QhSfBQEN7oOmUxiI9OkJmmh_96UFh8rN0nI-Ticew8A5xhdY8LwTfTqmtCaUMQOwBjXTFQCIXxY3rRpqpa2ZAROUvoon7TIx2CEWdMwQcUYzGfeZaeyCx5apXOIlfO9WZpy-AxzVD4NO3lh-gKaHnYbmOcGzs2yCNklOIVrF1cJOp9NSTPA6LqQwsLA4hE3MLlsTsGRVUMyZ_t7At4e7l-nT9Xzy-Nsevdc6ZqzXDGtFUdK97yzSnBNuG6ZRaJDijaEthTxThDdK8Rr1FmCsUWNFsS2oiEWaToBtzvf5aorifU2gRrkMrqFihsZlJN_Fe_m8j2sJa5rJDAtBpd7gxg-VyZluXBJm2FQ3oRVkoyLssSW_AtijhtSC1TAqx2oY0gpGvudBiO5rVCWpcl9hYW--D3AD7vvjH4Bs1-ajQ</recordid><startdate>20060501</startdate><enddate>20060501</enddate><creator>Lancaster, Alissa M</creator><creator>Jan, Eric</creator><creator>Sarnow, Peter</creator><general>Cold Spring Harbor Laboratory Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20060501</creationdate><title>Initiation factor-independent translation mediated by the hepatitis C virus internal ribosome entry site</title><author>Lancaster, Alissa M ; Jan, Eric ; Sarnow, Peter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c476t-6cca70acd7bfa97c27c86f09b0a35238307b92cda0740bf211f05c92f8952f0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Aminoacylation</topic><topic>Animals</topic><topic>Cattle</topic><topic>Centrifugation, Density Gradient</topic><topic>Codon, Initiator</topic><topic>Cricket paralysis virus</topic><topic>Dicistrovirus</topic><topic>Edeine - pharmacology</topic><topic>HeLa Cells</topic><topic>Hepacivirus - physiology</topic><topic>Hepatitis C virus</topic><topic>Humans</topic><topic>Liver - metabolism</topic><topic>Magnesium - pharmacology</topic><topic>Peptide Chain Initiation, Translational</topic><topic>Peptide Initiation Factors</topic><topic>Protein Biosynthesis</topic><topic>Ribosomes - metabolism</topic><topic>RNA, Transfer - metabolism</topic><topic>RNA, Viral - physiology</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lancaster, Alissa M</creatorcontrib><creatorcontrib>Jan, Eric</creatorcontrib><creatorcontrib>Sarnow, Peter</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>RNA (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lancaster, Alissa M</au><au>Jan, Eric</au><au>Sarnow, Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Initiation factor-independent translation mediated by the hepatitis C virus internal ribosome entry site</atitle><jtitle>RNA (Cambridge)</jtitle><addtitle>RNA</addtitle><date>2006-05-01</date><risdate>2006</risdate><volume>12</volume><issue>5</issue><spage>894</spage><epage>902</epage><pages>894-902</pages><issn>1355-8382</issn><eissn>1469-9001</eissn><abstract>The hepatitis C viral mRNA initiates translation using an internal ribosome entry site (IRES) located in the 5' noncoding region of the viral genome. At physiological magnesium ion concentrations, the HCV IRES forms a binary complex with the 40S ribosomal subunit, recruits initiation factor eIF3 and the ternary eIF2/GTP/Met-tRNA(i)Met complex, and joins 60S subunits to assemble translation-competent 80S ribosomes. Here we show that in the presence of 5 mM MgCl2, the HCV IRES can initiate translation by an alternative mechanism that does not require known initiation factors. Specifically, the HCV IRES was shown to initiate translation in a reconstituted system consisting only of purified 40S and 60S subunits, elongation factors, and aminoacylated tRNAs at high magnesium concentration. Analyses of assembled complexes supported a mechanism by which preformed 80S ribosomes can assemble directly on the HCV IRES at high cation concentrations. This mechanism is reminiscent of that employed by the divergent IRES elements in the Dicistroviridae, exemplified by the cricket paralysis virus, which mediates initiation of protein synthesis without initiator tRNA.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>16556939</pmid><doi>10.1261/rna.2342306</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Aminoacylation Animals Cattle Centrifugation, Density Gradient Codon, Initiator Cricket paralysis virus Dicistrovirus Edeine - pharmacology HeLa Cells Hepacivirus - physiology Hepatitis C virus Humans Liver - metabolism Magnesium - pharmacology Peptide Chain Initiation, Translational Peptide Initiation Factors Protein Biosynthesis Ribosomes - metabolism RNA, Transfer - metabolism RNA, Viral - physiology Transcription, Genetic |
| title | Initiation factor-independent translation mediated by the hepatitis C virus internal ribosome entry site |
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