The stimulation of gene expression by the R region from HTLV-1 and BLV

• Published in: Journal of biotechnology 2000-02, Vol.77 (2), p.179-189
• Main Authors: Attal, Joe, Théron, Marie-Claire, Kann, Guy, Bolifraud, Philippe, Puissant, Claudine, Houdebine, Louis Marie
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions; AIDS/HIV; Animals; Biological and medical sciences; Biotechnology; BLV; Bovine leukemia virus; Cells; CHO Cells; COS Cells; Cricetinae; Enhancer Elements, Genetic; Fundamental and applied biological sciences. Psychology; Gene Expression; Genes; Genetic engineering; Genetic technics; HeLa Cells; HTLV-1; Human T-lymphotropic virus 1; Human T-lymphotropic virus 1 - genetics; Humans; Leukemia Virus, Bovine - genetics; Life Sciences; Methods. Procedures. Technologies; Modification of gene expression level; Promoter Regions, Genetic; R region; RNA; RNA, Messenger - metabolism; simian virus 40; Simian virus 40 - genetics; Transfection; Viruses
• ISSN: 0168-1656; 1873-4863
• DOI: 10.1016/S0168-1656(99)00221-7

The 5′ untranslated regions (5′UTR) of mRNA are known to stimulate or inhibit more or less translation. SRα, an association of SV40 early gene promoter and of the R region plus the first 39 nucleotides of the U5 region (designated as R) from the human T-cell leukemia virus (HTLV-1) is currently used to stimulate expression of various coding regions. Its effect is considered to take place at the translational level. In all studies published so far, the R region was associated with the promoter and 5′UTR from SV40 early genes. In the present work, the role of SV40 5′UTR and HTLV-1R region was evaluated separately using different promoters, reporter genes and cells. Both SV40 5′UTR (SU) and R region (R) from HTLV-1 stimulated separately the expression of adjacent reporter genes. When associated, the SV40 5′UTR and the R region from HTLV-1 (SUR) were a more potent stimulator of gene expression and their effects were more than additive. This effect was very potent in HeLa and HC11 cells and almost inexistent in CHO and COS 7 cells. It was of various intensity in other cell types including bird and fish cells. The presence of SUR in gene constructs favoured the accumulation of the mRNAs. SUR stimulated gene expression when added between the cap and the initiation codon. Unexpectedly, SUR was never inhibitory. SUR can therefore be considered essentially as a potent and specific stimulator of gene expression favoring mRNA accumulation.