Context Dependence of Different Modules for Posttranscriptional Enhancement of Gene Expression from Retroviral Vectors
Abstract
We present a systematic comparison of three modules that enhance expression from retroviral gene transfer vectors at a posttranscriptional level: (i) splice signals (SS) that create an intron in the 5' untranslated region; (ii) constitutive RNA transport elements (CTE), originally discovered in D-type retroviruses; and (iii) the posttranscriptional regulatory element of woodchuck hepatitis virus (WPRE). Here we show that enhancement of expression depends not only on the specific element, but also on the gene of interest, implying context-dependent activity of the RNA elements. Interestingly, different results were obtained for genes that normally require or do not require such control elements. Expression of the HIV-1 gag-protease gene, which normally depends on the viral export factor Rev, was strongly enhanced by an oligomeric CTE, while WPRE had only a marginal effect. On the other hand, both CTE and WPRE compensated for the lack of an intron in the expression of human beta-globin. In this case, the strongest stimulation of RNA production was observed when functional SS were combined with the WPRE. Both CTE and, in particular, WPRE also enhanced expression of cDNAs that do not normally require any such element (green fluorescent protein, human multidrug resistance-1). In this study, functional SS and WPRE acted in an additive manner, resulting in a 10-fold higher level of expression. Our results indicate that the described modules act on different levels of RNA processing, transport, and translation and that the correct choice of a posttranscriptional enhancer configuration depends on the type of cDNA to be expressed.
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BibTeX
@article{schambach2026context,
title = {{Context Dependence of Different Modules for Posttranscriptional Enhancement of Gene Expression from Retroviral Vectors}},
author = {Axel Schambach and Harald Wodrich and Markus Hildinger and Jens Bohne and Hans-Georg Kräusslich and Christopher Baum},
journal = {Molecular Therapy},
year = {2026},
month = oct,
doi = {10.1006/mthe.2000.0191},
url = {https://hal.science/hal-05784097v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Context Dependence of Different Modules for Posttranscriptional Enhancement of Gene Expression from Retroviral Vectors
AU - Axel Schambach
AU - Harald Wodrich
AU - Markus Hildinger
AU - Jens Bohne
AU - Hans-Georg Kräusslich
AU - Christopher Baum
PY - 2026
DA - 2026/10/07
JO - Molecular Therapy
DO - 10.1006/mthe.2000.0191
UR - https://hal.science/hal-05784097v1
AB - We present a systematic comparison of three modules that enhance expression from retroviral gene transfer vectors at a posttranscriptional level: (i) splice signals (SS) that create an intron in the 5' untranslated region; (ii) constitutive RNA transport elements (CTE), originally discovered in D-type retroviruses; and (iii) the posttranscriptional regulatory element of woodchuck hepatitis virus (WPRE). Here we show that enhancement of expression depends not only on the specific element, but also on the gene of interest, implying context-dependent activity of the RNA elements. Interestingly, different results were obtained for genes that normally require or do not require such control elements. Expression of the HIV-1 gag-protease gene, which normally depends on the viral export factor Rev, was strongly enhanced by an oligomeric CTE, while WPRE had only a marginal effect. On the other hand, both CTE and WPRE compensated for the lack of an intron in the expression of human beta-globin. In this case, the strongest stimulation of RNA production was observed when functional SS were combined with the WPRE. Both CTE and, in particular, WPRE also enhanced expression of cDNAs that do not normally require any such element (green fluorescent protein, human multidrug resistance-1). In this study, functional SS and WPRE acted in an additive manner, resulting in a 10-fold higher level of expression. Our results indicate that the described modules act on different levels of RNA processing, transport, and translation and that the correct choice of a posttranscriptional enhancer configuration depends on the type of cDNA to be expressed.
SN - 1525-0016
SN - 1525-0024
ER -