Leucine-tRNA Initiates at CUG Start Codons for Protein Synthesis and Presentation by MHC Class I
Effective immune surveillance by cytotoxic T cells requires newly synthesized polypeptides for presentation by major histocompatibility complex (MHC) class I molecules. These polypeptides are produced not only from conventional AUG-initiated, but also from cryptic non-AUG-initiated, reading frames b...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2012-06, Vol.336 (6089), p.1719-1723 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Starck, Shelley R. Jiang, Vivian Pavon-Eternod, Mariana Prasad, Sharanya McCarthy, Brian Pan, Tao Shastri, Nilabh |
| description | Effective immune surveillance by cytotoxic T cells requires newly synthesized polypeptides for presentation by major histocompatibility complex (MHC) class I molecules. These polypeptides are produced not only from conventional AUG-initiated, but also from cryptic non-AUG-initiated, reading frames by distinct translational mechanisms. Biochemical analysis of ribosomal initiation complexes at CUG versus AUG initiation codons revealed that cells use an elongator leucine-bound transfer RNA (Leu-tRNA) to initiate translation at cryptic CUG start codons. CUG/Leu-tRNA initiation was independent of the canonical initiator tRNA (AUG/Met-tRNA i Met ) pathway but required expression of eukaryotic initiation factor 2A. Thus, a tRNA-based translation initiation mechanism allows non-AUG-initiated protein synthesis and supplies peptides for presentation by MHC class I molecules. |
| doi_str_mv | 10.1126/science.1220270 |
| format | Article |
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These polypeptides are produced not only from conventional AUG-initiated, but also from cryptic non-AUG-initiated, reading frames by distinct translational mechanisms. Biochemical analysis of ribosomal initiation complexes at CUG versus AUG initiation codons revealed that cells use an elongator leucine-bound transfer RNA (Leu-tRNA) to initiate translation at cryptic CUG start codons. CUG/Leu-tRNA initiation was independent of the canonical initiator tRNA (AUG/Met-tRNA i Met ) pathway but required expression of eukaryotic initiation factor 2A. Thus, a tRNA-based translation initiation mechanism allows non-AUG-initiated protein synthesis and supplies peptides for presentation by MHC class I molecules.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1220270</identifier><identifier>PMID: 22745432</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Animals ; Antigen Presentation - genetics ; Antigen-Presenting Cells - immunology ; Biochemistry ; Biological and medical sciences ; Cercopithecus aethiops ; Codon, Initiator ; COS Cells ; Elongation ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Genetics of the immune response ; HeLa Cells ; Histocompatibility Antigens Class I - genetics ; Histocompatibility Antigens Class I - immunology ; Humans ; Hybridomas ; Hybridomas - immunology ; Immune system ; Immunobiology ; Leucine ; Messenger RNA ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Molecules ; Open reading frames ; Peptide Chain Initiation, Translational ; Polypeptides ; Protein Biosynthesis - genetics ; Protein synthesis ; Proteins ; Ribonucleic acids ; Ribosomes ; RNA, Transfer, Leu ; RNA-protein interactions ; Start codon ; Stem cells ; T lymphocytes ; T-Lymphocytes - immunology ; Textbooks ; Transfer RNA ; Translation ; Translations</subject><ispartof>Science (American Association for the Advancement of Science), 2012-06, Vol.336 (6089), p.1719-1723</ispartof><rights>Copyright © 2012 American Association for the Advancement of Science</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-963a390aa3948c874f6c0f9db180c95666ea63cfe1134bca6b2edd17c3f99b073</citedby><cites>FETCH-LOGICAL-c509t-963a390aa3948c874f6c0f9db180c95666ea63cfe1134bca6b2edd17c3f99b073</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41585174$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41585174$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26074309$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22745432$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Starck, Shelley R.</creatorcontrib><creatorcontrib>Jiang, Vivian</creatorcontrib><creatorcontrib>Pavon-Eternod, Mariana</creatorcontrib><creatorcontrib>Prasad, Sharanya</creatorcontrib><creatorcontrib>McCarthy, Brian</creatorcontrib><creatorcontrib>Pan, Tao</creatorcontrib><creatorcontrib>Shastri, Nilabh</creatorcontrib><title>Leucine-tRNA Initiates at CUG Start Codons for Protein Synthesis and Presentation by MHC Class I</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Effective immune surveillance by cytotoxic T cells requires newly synthesized polypeptides for presentation by major histocompatibility complex (MHC) class I molecules. These polypeptides are produced not only from conventional AUG-initiated, but also from cryptic non-AUG-initiated, reading frames by distinct translational mechanisms. Biochemical analysis of ribosomal initiation complexes at CUG versus AUG initiation codons revealed that cells use an elongator leucine-bound transfer RNA (Leu-tRNA) to initiate translation at cryptic CUG start codons. CUG/Leu-tRNA initiation was independent of the canonical initiator tRNA (AUG/Met-tRNA i Met ) pathway but required expression of eukaryotic initiation factor 2A. Thus, a tRNA-based translation initiation mechanism allows non-AUG-initiated protein synthesis and supplies peptides for presentation by MHC class I molecules.</description><subject>Animals</subject><subject>Antigen Presentation - genetics</subject><subject>Antigen-Presenting Cells - immunology</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Cercopithecus aethiops</subject><subject>Codon, Initiator</subject><subject>COS Cells</subject><subject>Elongation</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Genetics of the immune response</subject><subject>HeLa Cells</subject><subject>Histocompatibility Antigens Class I - genetics</subject><subject>Histocompatibility Antigens Class I - immunology</subject><subject>Humans</subject><subject>Hybridomas</subject><subject>Hybridomas - immunology</subject><subject>Immune system</subject><subject>Immunobiology</subject><subject>Leucine</subject><subject>Messenger RNA</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Molecules</subject><subject>Open reading frames</subject><subject>Peptide Chain Initiation, Translational</subject><subject>Polypeptides</subject><subject>Protein Biosynthesis - genetics</subject><subject>Protein synthesis</subject><subject>Proteins</subject><subject>Ribonucleic acids</subject><subject>Ribosomes</subject><subject>RNA, Transfer, Leu</subject><subject>RNA-protein interactions</subject><subject>Start codon</subject><subject>Stem cells</subject><subject>T lymphocytes</subject><subject>T-Lymphocytes - immunology</subject><subject>Textbooks</subject><subject>Transfer RNA</subject><subject>Translation</subject><subject>Translations</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0c9rFDEUB_AgFrtWz56UgAheps3vmRzLoO3Ctoq15zGTeYNZZpM2yRz2vzd1xwq9lEASkk8evHwRekfJKaVMnSXrwFs4pYwRVpMXaEWJlpVmhL9EK0K4qhpSy2P0OqUtIeVO81fomLFaSMHZCv3awGydhyr_uD7Ha--yMxkSNhm3txf4JptYdmEIPuExRPw9hgzO45u9z78huSL9UE4hgc8mu-Bxv8dXly1uJ5MSXr9BR6OZErxd1hN0-_XLz_ay2ny7WLfnm8pKonOlFTdcE1Mm0dimFqOyZNRDTxtitVRKgVHcjkApF701qmcwDLS2fNS6JzU_QZ8Pde9iuJ8h5W7nkoVpMh7CnLpSpwwhJHmeSkmVYOW3nqeEsUY0StFCPz6h2zBHX3p-ULyWpTFe1NlB2RhSijB2d9HtTNwX1D1E2i2Rdkuk5cWHpe7c72B49P8yLODTAkyyZhqj8dal_06RWvC_vbw_uG3KIT7eCyobSQv5A8C6sPs</recordid><startdate>20120629</startdate><enddate>20120629</enddate><creator>Starck, Shelley R.</creator><creator>Jiang, Vivian</creator><creator>Pavon-Eternod, Mariana</creator><creator>Prasad, Sharanya</creator><creator>McCarthy, Brian</creator><creator>Pan, Tao</creator><creator>Shastri, Nilabh</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>IQODW</scope><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>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20120629</creationdate><title>Leucine-tRNA Initiates at CUG Start Codons for Protein Synthesis and Presentation by MHC Class I</title><author>Starck, Shelley R. ; Jiang, Vivian ; Pavon-Eternod, Mariana ; Prasad, Sharanya ; McCarthy, Brian ; Pan, Tao ; Shastri, Nilabh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-963a390aa3948c874f6c0f9db180c95666ea63cfe1134bca6b2edd17c3f99b073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antigen Presentation - genetics</topic><topic>Antigen-Presenting Cells - immunology</topic><topic>Biochemistry</topic><topic>Biological and medical sciences</topic><topic>Cercopithecus aethiops</topic><topic>Codon, Initiator</topic><topic>COS Cells</topic><topic>Elongation</topic><topic>Fundamental and applied biological sciences. 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Academic</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Starck, Shelley R.</au><au>Jiang, Vivian</au><au>Pavon-Eternod, Mariana</au><au>Prasad, Sharanya</au><au>McCarthy, Brian</au><au>Pan, Tao</au><au>Shastri, Nilabh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leucine-tRNA Initiates at CUG Start Codons for Protein Synthesis and Presentation by MHC Class I</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2012-06-29</date><risdate>2012</risdate><volume>336</volume><issue>6089</issue><spage>1719</spage><epage>1723</epage><pages>1719-1723</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Effective immune surveillance by cytotoxic T cells requires newly synthesized polypeptides for presentation by major histocompatibility complex (MHC) class I molecules. These polypeptides are produced not only from conventional AUG-initiated, but also from cryptic non-AUG-initiated, reading frames by distinct translational mechanisms. Biochemical analysis of ribosomal initiation complexes at CUG versus AUG initiation codons revealed that cells use an elongator leucine-bound transfer RNA (Leu-tRNA) to initiate translation at cryptic CUG start codons. CUG/Leu-tRNA initiation was independent of the canonical initiator tRNA (AUG/Met-tRNA i Met ) pathway but required expression of eukaryotic initiation factor 2A. Thus, a tRNA-based translation initiation mechanism allows non-AUG-initiated protein synthesis and supplies peptides for presentation by MHC class I molecules.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>22745432</pmid><doi>10.1126/science.1220270</doi><tpages>5</tpages></addata></record> |
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| ispartof | Science (American Association for the Advancement of Science), 2012-06, Vol.336 (6089), p.1719-1723 |
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| subjects | Animals Antigen Presentation - genetics Antigen-Presenting Cells - immunology Biochemistry Biological and medical sciences Cercopithecus aethiops Codon, Initiator COS Cells Elongation Fundamental and applied biological sciences. Psychology Fundamental immunology Genetics of the immune response HeLa Cells Histocompatibility Antigens Class I - genetics Histocompatibility Antigens Class I - immunology Humans Hybridomas Hybridomas - immunology Immune system Immunobiology Leucine Messenger RNA Mice Mice, Inbred C57BL Mice, Transgenic Molecules Open reading frames Peptide Chain Initiation, Translational Polypeptides Protein Biosynthesis - genetics Protein synthesis Proteins Ribonucleic acids Ribosomes RNA, Transfer, Leu RNA-protein interactions Start codon Stem cells T lymphocytes T-Lymphocytes - immunology Textbooks Transfer RNA Translation Translations |
| title | Leucine-tRNA Initiates at CUG Start Codons for Protein Synthesis and Presentation by MHC Class I |
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