Abstract
A genetic screen previously identified the N-terminal 91 amino acids of the eukaryotic initiation factor 3 subunit f (N91-eIF3f) as a potent inhibitor of HIV-1 replication. Overexpression of N91-eIF3f or full-length eIF3f reduced the level of HIV-1 mRNAs in the infected cell. Here we show that N91-eIF3f and eIF3f act by specifically blocking the 3' end processing of the HIV-1 pre-mRNA both in vivo and in vitro. Furthermore, the results suggest that eIF3f mediates this restriction of HIV-1 expression through the previously unsuspected involvement of a set of factors that includes eIF3f, the SR protein 9G8, and the cyclin-dependent kinase 11 (CDK11). eIF3f affects HIV-1 3' end processing by modulating the sequence-specific recognition of the HIV-1 pre-mRNA by 9G8.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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Binding Sites
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Cell Extracts
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Cell Nucleus / metabolism
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Cyclin-Dependent Kinases / metabolism*
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Eukaryotic Initiation Factor-3 / chemistry
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Eukaryotic Initiation Factor-3 / metabolism*
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HIV Long Terminal Repeat / genetics
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HIV-1 / genetics*
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HIV-1 / physiology
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HeLa Cells
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Humans
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Models, Biological
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Molecular Sequence Data
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Nuclear Proteins
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Nucleocytoplasmic Transport Proteins / metabolism*
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Poly A / metabolism
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Protein Binding
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RNA 3' End Processing / genetics*
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RNA, Messenger / metabolism
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RNA, Viral / metabolism*
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RNA-Binding Proteins / metabolism*
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Serine-Arginine Splicing Factors
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Virus Replication
Substances
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Cell Extracts
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Eukaryotic Initiation Factor-3
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Nuclear Proteins
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Nucleocytoplasmic Transport Proteins
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RNA, Messenger
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RNA, Viral
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RNA-Binding Proteins
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Serine-Arginine Splicing Factors
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Poly A
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CDK11a protein, human
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Cyclin-Dependent Kinases