Linked Life Data

10900014

Source:http://linkedlifedata.com/resource/pubmed/id/10900014

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2000-8-24
pubmed:databankReference
pubmed:abstractText
The 5'-untranslated region of hepatitis C virus (HCV) is highly conserved, folds into a complex secondary structure, and functions as an internal ribosome entry site (IRES) to initiate translation of HCV proteins. We have developed a selection system based on a randomized hairpin ribozyme gene library to identify cellular factors involved in HCV IRES function. A retroviral vector ribozyme library with randomized target recognition sequences was introduced into HeLa cells, stably expressing a bicistronic construct encoding the hygromycin B phosphotransferase gene and the herpes simplex virus thymidine kinase gene (HSV-tk). Translation of the HSV-tk gene was mediated by the HCV IRES. Cells expressing ribozymes that inhibit HCV IRES-mediated translation of HSV-tk were selected via their resistance to both ganciclovir and hygromycin B. Two ribozymes reproducibly conferred the ganciclovir-resistant phenotype and were shown to inhibit IRES-mediated translation of HCV core protein but did not inhibit cap-dependent protein translation or cell growth. The functional targets of these ribozymes were identified as the gamma subunits of human eukaryotic initiation factors 2B (eIF2Bgamma) and 2 (eIF2gamma), respectively. The involvement of eIF2Bgamma and eIF2gamma in HCV IRES-mediated translation was further validated by ribozymes directed against additional sites within the mRNAs of these genes. In addition to leading to the identification of cellular IRES cofactors, ribozymes obtained from this cellular selection system could be directly used to specifically inhibit HCV viral translation, thereby facilitating the development of new antiviral strategies for HCV infection.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-10432456, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-1647211, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-1956383, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-2660906, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-6248551, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-6302704, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-7555089, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-7666538, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-8643645, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-8809057, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-8846793, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-8971007, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-8981917, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-8995696, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-9023100, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-9044745, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-9122180, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-9252077, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-9254694, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-9282175, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-9420332, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-9472020, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-9573242, http://linkedlifedata.com/resource/pubmed/commentcorrection/10900014-9722591
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8566-71
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:10900014-5' Untranslated Regions, pubmed-meshheading:10900014-Animals, pubmed-meshheading:10900014-Base Sequence, pubmed-meshheading:10900014-Cell Line, pubmed-meshheading:10900014-DNA, Complementary, pubmed-meshheading:10900014-Dogs, pubmed-meshheading:10900014-Eukaryotic Initiation Factor-2, pubmed-meshheading:10900014-Eukaryotic Initiation Factor-2B, pubmed-meshheading:10900014-HeLa Cells, pubmed-meshheading:10900014-Hepacivirus, pubmed-meshheading:10900014-Humans, pubmed-meshheading:10900014-Molecular Sequence Data, pubmed-meshheading:10900014-Protein Biosynthesis, pubmed-meshheading:10900014-RNA, Catalytic, pubmed-meshheading:10900014-RNA, Messenger, pubmed-meshheading:10900014-RNA Caps, pubmed-meshheading:10900014-Ribosomes, pubmed-meshheading:10900014-Viral Core Proteins
pubmed:year
2000
pubmed:articleTitle
Identification of eIF2Bgamma and eIF2gamma as cofactors of hepatitis C virus internal ribosome entry site-mediated translation using a functional genomics approach.
pubmed:affiliation
Department of Medicine, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA, 92093-0665, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't