Sam68 is absolutely required for Rev function and HIV-1 production
| Autor: | Suhasini, Modem, Kameswara R, Badri, Thomas C, Holland, Thipparthi R, Reddy |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Gene Expression Regulation
Viral Transcriptional Activation viruses Response Elements RNA Transport Article Cell Line 03 medical and health sciences 0302 clinical medicine Genes Reporter Genetics Humans RNA Messenger Adaptor Proteins Signal Transducing 030304 developmental biology 0303 health sciences RNA-Binding Proteins rev Gene Products Human Immunodeficiency Virus Phosphoproteins 3. Good health DNA-Binding Proteins Gene Products rev 030220 oncology & carcinogenesis HIV-1 RNA Viral RNA Interference HeLa Cells |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 |
| DOI: | 10.1093/nar/gki231 |
| Popis: | Sam68 functionally complements for, as well as synergizes with, HIV-1 Rev in Rev response element (RRE)-mediated gene expression and virus production. Furthermore, C-terminal deletion/point mutants of Sam68 (Sam68DeltaC/Sam68-P21) exert a transdominant negative phenotype for Rev function and HIV-1 production. However, the relevance of Sam68 in Rev/RRE function is not well defined. To gain more insight into the mechanism of Sam68 in Rev function, we used an RNAi (RNA interference) strategy to create stable Sam68 knockdown HeLa (SSKH) cells. In SSKH cells, Rev failed to activate both RRE-mediated reporter gene [chloramphenicol acetyltransferase (CAT) and/or gag] expressions. Importantly, reduction of Sam68 expression led to a dramatic inhibition of HIV-1 production. Inhibition of the reporter gene expression and HIV production correlated with the failure to export RRE-containing CAT mRNA and unspliced viral mRNAs to the cytoplasm, confirming that SSKH cells are defective for Rev-mediated RNA export. Taken together, these results suggest that Sam68 is involved in Rev-mediated RNA export and is absolutely required for HIV production. |
| Databáze: | OpenAIRE |
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