TY  - JOUR
A1  - Bodem, Jochen
A1  - Schrom, Eva-Maria
A1  - Moschall, Rebecca
A1  - Hartl, Maximilian J.
A1  - Weitner, Helena
A1  - Fecher, David
A1  - Langemeier, Jörg
A1  - Wöhrl, Brigitta M.
T1  - U1snRNP-mediated suppression of polyadenylation in conjunction with the RNA structure controls poly (A) site selection in foamy viruses
JF  - Retrovirology
N2  - Background

During reverse transcription, retroviruses duplicate the long terminal repeats (LTRs). These identical LTRs carry both promoter regions and functional polyadenylation sites. To express full-length transcripts, retroviruses have to suppress polyadenylation in the 5′LTR and activate polyadenylation in the 3′LTR. Foamy viruses have a unique LTR structure with respect to the location of the major splice donor (MSD), which is located upstream of the polyadenylation signal.

Results

Here, we describe the mechanisms of foamy viruses regulating polyadenylation. We show that binding of the U1 small nuclear ribonucleoprotein (U1snRNP) to the MSD suppresses polyadenylation at the 5′LTR. In contrast, polyadenylation at the 3′LTR is achieved by adoption of a different RNA structure at the MSD region, which blocks U1snRNP binding and furthers RNA cleavage and subsequent polyadenylation.

Conclusion

Recently, it was shown that U1snRNP is able to suppress the usage of intronic cryptic polyadenylation sites in the cellular genome. Foamy viruses take advantage of this surveillance mechanism to suppress premature polyadenylation at the 5’end of their RNA. At the 3’end, Foamy viruses use a secondary structure to presumably block access of U1snRNP and thereby activate polyadenylation at the end of the genome. Our data reveal a contribution of U1snRNP to cellular polyadenylation site selection and to the regulation of gene expression.
KW  - Polyadenylation
KW  - foamy virus
KW  - RNA structure
KW  - Major splice donor
KW  - Polyadenylierung
KW  - RNS
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96085
UR  - http://www.retrovirology.com/content/10/1/55
ER  - 
TY  - JOUR
A1  - Fecher, David
A1  - Hofmann, Elisabeth
A1  - Buck, Andreas
A1  - Bundschuh, Ralph
A1  - Nietzer, Sarah
A1  - Dandekar, Gudrun
A1  - Walles, Thorsten
A1  - Walles, Heike
A1  - Lückerath, Katharina
A1  - Steinke, Maria
T1  - Human Organotypic Lung Tumor Models: Suitable For Preclinical \(^{18}\)F-FDG PET-Imaging
JF  - PLoS ONE
N2  - Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and –testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[\(^{18}\)F]fluoro-D-glucose positron emission tomography (FDG-PET) these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future.
KW  - lung and intrathoracic tumors
KW  - trachea
KW  - adenocarcinoma of the lung
KW  - cancer treatment
KW  - secondary lung tumors
KW  - pulmonary imaging
KW  - extracellular matrix
KW  - collagens
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-179678
VL  - 11
IS  - 8
ER  -