Functional and structural analysis of the internal ribosome entry site present in the mRNA of natural variants of the HIV-1
The 5'untranslated regions (UTR) of the full length mRNA of the HIV-1 proviral clones pNL4.3 and pLAI, harbor an internal ribosomal entry site (IRES). In this study we extend this finding by demonstrating that the mRNA 5'UTRs of natural variants of HIV-1 also exhibit IRES-activity. Cap-ind...
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| description | The 5'untranslated regions (UTR) of the full length mRNA of the HIV-1 proviral clones pNL4.3 and pLAI, harbor an internal ribosomal entry site (IRES). In this study we extend this finding by demonstrating that the mRNA 5'UTRs of natural variants of HIV-1 also exhibit IRES-activity. Cap-independent translational activity was demonstrated using bicistronic mRNAs in HeLa cells and in Xenopus laevis oocytes. The possibility that expression of the downstream cistron in these constructs was due to alternative splicing or to cryptic promoter activity was ruled out. The HIV-1 variants exhibited significant 5'UTR nucleotide diversity with respect to the control sequence recovered from pNL4.3. Interestingly, translational activity from the 5'UTR of some of the HIV-1 variants was enhanced relative to that observed for the 5'UTR of pNL4.3. In an attempt to explain these findings we probed the secondary structure of the variant HIV-1 5'UTRs using enzymatic and chemical approaches. Yet subsequent structural analyses did not reveal significant variations when compared to the pNL4.3-5'UTR. Thus, the increased IRES-activity observed for some of the HIV-1 variants cannot be ascribed to a specific structural modification. A model to explain these findings is proposed. |
| doi_str_mv | 10.1371/journal.pone.0035031 |
| format | Article |
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In this study we extend this finding by demonstrating that the mRNA 5'UTRs of natural variants of HIV-1 also exhibit IRES-activity. Cap-independent translational activity was demonstrated using bicistronic mRNAs in HeLa cells and in Xenopus laevis oocytes. The possibility that expression of the downstream cistron in these constructs was due to alternative splicing or to cryptic promoter activity was ruled out. The HIV-1 variants exhibited significant 5'UTR nucleotide diversity with respect to the control sequence recovered from pNL4.3. Interestingly, translational activity from the 5'UTR of some of the HIV-1 variants was enhanced relative to that observed for the 5'UTR of pNL4.3. In an attempt to explain these findings we probed the secondary structure of the variant HIV-1 5'UTRs using enzymatic and chemical approaches. Yet subsequent structural analyses did not reveal significant variations when compared to the pNL4.3-5'UTR. Thus, the increased IRES-activity observed for some of the HIV-1 variants cannot be ascribed to a specific structural modification. A model to explain these findings is proposed.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0035031</identifier><identifier>PMID: 22496887</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>5' Untranslated Regions ; Alternative splicing ; Analysis ; Biology ; Cell cycle ; Cistrons ; Cloning ; HeLa Cells ; HIV ; HIV-1 - metabolism ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Humans ; Internal ribosome entry site ; Medicine ; Messenger RNA ; Models, Biological ; mRNA ; Nucleic Acid Conformation ; Nucleotide sequence ; Oocytes ; Plasmids ; Promoters ; Protein Biosynthesis ; Protein structure ; Protein synthesis ; Proteins ; Recruitment ; Ribosomes - metabolism ; RNA, Messenger - metabolism ; RNA, Viral - blood ; Secondary structure ; Structural analysis ; Structure-function relationships ; Translation ; Xenopus ; Xenopus laevis</subject><ispartof>PloS one, 2012-04, Vol.7 (4), p.e35031-e35031</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Vallejos et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Vallejos et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-9c07b851c9f5bd12f0d590a6751ac7b2ec5d3f0dc6cb85ef13f09574dfa59f233</citedby><cites>FETCH-LOGICAL-c725t-9c07b851c9f5bd12f0d590a6751ac7b2ec5d3f0dc6cb85ef13f09574dfa59f233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319624/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319624/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22496887$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Jang, Sung Key</contributor><creatorcontrib>Vallejos, Maricarmen</creatorcontrib><creatorcontrib>Carvajal, Felipe</creatorcontrib><creatorcontrib>Pino, Karla</creatorcontrib><creatorcontrib>Navarrete, Camilo</creatorcontrib><creatorcontrib>Ferres, Marcela</creatorcontrib><creatorcontrib>Huidobro-Toro, Juan Pablo</creatorcontrib><creatorcontrib>Sargueil, Bruno</creatorcontrib><creatorcontrib>López-Lastra, Marcelo</creatorcontrib><title>Functional and structural analysis of the internal ribosome entry site present in the mRNA of natural variants of the HIV-1</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The 5'untranslated regions (UTR) of the full length mRNA of the HIV-1 proviral clones pNL4.3 and pLAI, harbor an internal ribosomal entry site (IRES). In this study we extend this finding by demonstrating that the mRNA 5'UTRs of natural variants of HIV-1 also exhibit IRES-activity. Cap-independent translational activity was demonstrated using bicistronic mRNAs in HeLa cells and in Xenopus laevis oocytes. The possibility that expression of the downstream cistron in these constructs was due to alternative splicing or to cryptic promoter activity was ruled out. The HIV-1 variants exhibited significant 5'UTR nucleotide diversity with respect to the control sequence recovered from pNL4.3. Interestingly, translational activity from the 5'UTR of some of the HIV-1 variants was enhanced relative to that observed for the 5'UTR of pNL4.3. In an attempt to explain these findings we probed the secondary structure of the variant HIV-1 5'UTRs using enzymatic and chemical approaches. Yet subsequent structural analyses did not reveal significant variations when compared to the pNL4.3-5'UTR. Thus, the increased IRES-activity observed for some of the HIV-1 variants cannot be ascribed to a specific structural modification. A model to explain these findings is proposed.</description><subject>5' Untranslated Regions</subject><subject>Alternative splicing</subject><subject>Analysis</subject><subject>Biology</subject><subject>Cell cycle</subject><subject>Cistrons</subject><subject>Cloning</subject><subject>HeLa Cells</subject><subject>HIV</subject><subject>HIV-1 - metabolism</subject><subject>Human immunodeficiency virus</subject><subject>Human immunodeficiency virus 1</subject><subject>Humans</subject><subject>Internal ribosome entry site</subject><subject>Medicine</subject><subject>Messenger RNA</subject><subject>Models, Biological</subject><subject>mRNA</subject><subject>Nucleic Acid Conformation</subject><subject>Nucleotide sequence</subject><subject>Oocytes</subject><subject>Plasmids</subject><subject>Promoters</subject><subject>Protein Biosynthesis</subject><subject>Protein structure</subject><subject>Protein synthesis</subject><subject>Proteins</subject><subject>Recruitment</subject><subject>Ribosomes - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vallejos, Maricarmen</au><au>Carvajal, Felipe</au><au>Pino, Karla</au><au>Navarrete, Camilo</au><au>Ferres, Marcela</au><au>Huidobro-Toro, Juan Pablo</au><au>Sargueil, Bruno</au><au>López-Lastra, Marcelo</au><au>Jang, Sung Key</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional and structural analysis of the internal ribosome entry site present in the mRNA of natural variants of the HIV-1</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-04-04</date><risdate>2012</risdate><volume>7</volume><issue>4</issue><spage>e35031</spage><epage>e35031</epage><pages>e35031-e35031</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The 5'untranslated regions (UTR) of the full length mRNA of the HIV-1 proviral clones pNL4.3 and pLAI, harbor an internal ribosomal entry site (IRES). In this study we extend this finding by demonstrating that the mRNA 5'UTRs of natural variants of HIV-1 also exhibit IRES-activity. Cap-independent translational activity was demonstrated using bicistronic mRNAs in HeLa cells and in Xenopus laevis oocytes. The possibility that expression of the downstream cistron in these constructs was due to alternative splicing or to cryptic promoter activity was ruled out. The HIV-1 variants exhibited significant 5'UTR nucleotide diversity with respect to the control sequence recovered from pNL4.3. Interestingly, translational activity from the 5'UTR of some of the HIV-1 variants was enhanced relative to that observed for the 5'UTR of pNL4.3. In an attempt to explain these findings we probed the secondary structure of the variant HIV-1 5'UTRs using enzymatic and chemical approaches. Yet subsequent structural analyses did not reveal significant variations when compared to the pNL4.3-5'UTR. Thus, the increased IRES-activity observed for some of the HIV-1 variants cannot be ascribed to a specific structural modification. A model to explain these findings is proposed.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22496887</pmid><doi>10.1371/journal.pone.0035031</doi><tpages>e35031</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 5' Untranslated Regions Alternative splicing Analysis Biology Cell cycle Cistrons Cloning HeLa Cells HIV HIV-1 - metabolism Human immunodeficiency virus Human immunodeficiency virus 1 Humans Internal ribosome entry site Medicine Messenger RNA Models, Biological mRNA Nucleic Acid Conformation Nucleotide sequence Oocytes Plasmids Promoters Protein Biosynthesis Protein structure Protein synthesis Proteins Recruitment Ribosomes - metabolism RNA, Messenger - metabolism RNA, Viral - blood Secondary structure Structural analysis Structure-function relationships Translation Xenopus Xenopus laevis |
| title | Functional and structural analysis of the internal ribosome entry site present in the mRNA of natural variants of the HIV-1 |
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