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NCCR RNA & Disease
Third-party funded project |
Project title |
NCCR RNA & Disease |
Principal Investigator(s) |
Zavolan, Mihaela
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Project Members |
Azevedo Salgado Guimaraes, Joao Carlos Dimitriades, Beatrice Martin, Georges Schmidt, Ralf Jedlinski, Dominik Mittal, Nitish Pasulka, Josef Gnann, Alexandra Gypas, Foivos Todesco, Liliane Ghosh, Shreemoyee Ghosh, Souvik Mues, Lea
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Organisation / Research unit |
Departement Biozentrum / Bioinformatics (Zavolan) |
Project Website |
http://www.nccr-rna-and-disease.ch |
Project start |
01.05.2014 |
Probable end |
30.04.2018 |
Status |
Completed |
Abstract |
RNA as the central molecule of life
The last decades of research in molecular biology provided evidence that RNA (ribonucleic acid) is not a simple messenger between DNA (deoxyribonucleic acid) and proteins, but plays a central role in cellular processes. Growing consensus suggests that life originated as an ‘RNA world’ where RNA served as both, a carrier of genetic information and a biocatalyst. Fundamental processes such as for example the synthesis of proteins are catalyzed by RNA molecules in all existing organisms. In recent years, a tremendous number of non-coding (nc)RNAs and complex RNA-mediated pathways involved in gene regulation have been discovered. These findings underline the pivotal contribution of RNA to the overall regulation of eukaryotic gene expression.
RNA & Disease
Within a cell, various types of RNA molecules exert complex and multifaceted functions, involved in numerous cellular processes. It is therefore not surprising, that many diseases emerge from aberrant RNA processing or RNA-dependent dysreguation of gene expression. Many genetic disorders derive from mutations in non-coding genome regions and in RNA-binding proteins. In various cancers and metabolic diseases, changes in the level of ncRNAs and RNA-binding proteins can be observed. Remarkably, major diseases causing human death, including cardiac failure, cancer, neurodegeneration and metabolic diseases, are associated with malfunctioning RNA regulation. Many additional diseases are expected to be caused by yet unknown defects in RNA-based gene regulation. Understanding the molecular basis of RNA regulation is therefore essential to lead to better diagnostic tools, to the identification of new therapeutic targets as well as to new drugs. RNA is not only a therapeutic target, but can also itself serve as a drug. The discovery of small regulatory RNAs promoted research towards the application of small RNA molecules as highly specific therapeutics. A few RNA based drugs, e.g. for the treatment of homozygous familial hypercholesterolemia or neovascular age-related macular degeneration, are already on the market.
Goals of the NCCR RNA & Disease
- Establishing a Swiss RNA research focus that consolidates and reinforces the position of Switzerland in RNA biology by a coordinated, interdisciplinary research program.
- Building bridges between basic and medical research to promote rapid transition of new findings into medical applications
- Advancing our understanding of RNA processing and surveillance mechanisms involved in global regulation of mRNAs and ncRNAs.
- Identification of disease mechanisms resulting from aberrant RNA function.
- Development of possible therapeutic and diagnostic approaches.
Projects in the group of Mihaela Zavolan
In this large collaborative project we have two main sub-projects. The first aims to understand the connection between metabolism and aging and the role of the RNA regulatory layer therein. It is now well established that reduced caloric intake leads to improved metabolic parameters in a lot of organisms and that RNA binding proteins are involved in the process. To understand how we study model systems from yeast to mammalian cells in which the rate of aging is perturbed. The second sub-project follows observations that the length of regulatory regions (so-called 3’ untranslated regions, 3’UTRs) of messenger RNAs (mRNA) changes systematically during processes such as development or immune responses. Moreover, mRNAs with short 3’UTRs are prevalent in cancers. We aim to understand the mechanisms underlying this change, which is frequently implemented at the level of mRNA synthesis, by termination factors. |
Financed by |
Swiss National Science Foundation (SNSF) University of Basel
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Published results () |
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ID |
Autor(en) |
Titel |
ISSN / ISBN |
Erschienen in |
Art der Publikation |
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3567622 |
Gruber, Andreas J.; Schmidt, Ralf; Gruber, Andreas R.; Martin, Georges; Ghosh, Souvik; Belmadani, Manuel; Keller, Walter; Zavolan, Mihaela |
A comprehensive analysis of 3' end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogeneous ribonucleoprotein C on cleavage and polyadenylation |
1088-9051 ; 1549-5469 |
Genome Research |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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3975704 |
Martin, Georges; Schmidt, Ralf; Gruber, Andreas J.; Ghosh, Souvik; Keller, Walter; Zavolan, Mihaela |
3' End Sequencing Library Preparation with A-seq2 |
1940-087X |
Journal of Visualized Experiments |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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3892473 |
Mittal, Nitish; Guimaraes, Joao C.; Gross, Thomas; Schmidt, Alexander; Vina-Vilaseca, Arnau; Nedialkova, Danny D.; Aeschimann, Florian; Leidel, Sebastian A.; Spang, Anne; Zavolan, Mihaela |
The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan |
2041-1723 |
Nature Communications |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
|
4462735 |
Gruber, Andreas J.; Schmidt, Ralf; Ghosh, Souvik; Martin, Georges; Gruber, Andreas R.; van Nimwegen, Erik; Zavolan, Mihaela |
Discovery of physiological and cancer-related regulators of 3' UTR processing with KAPAC |
1474-760X |
Genome biology |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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4487372 |
Gruber, Andreas J.; Gypas, Foivos; Riba, Andrea; Schmidt, Ralf; Zavolan, Mihaela |
Terminal exon characterization with TECtool reveals an abundance of cell-specific isoforms |
1548-7105 |
Nature methods |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
|
4515423 |
Herrmann, Christina J.; Schmidt, Ralf; Kanitz, Alexander; Artimo, Panu; Gruber, Andreas J.; Zavolan, Mihaela |
PolyASite 2.0: a consolidated atlas of polyadenylation sites from 3' end sequencing |
0305-1048 ; 1362-4962 |
Nucleic acids research |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
|
4525817 |
Liko, Dritan; Rzepiela, Andrzej; Vukojevic, Vanja; Zavolan, Mihaela; Hall, Michael N. |
Loss of TSC complex enhances gluconeogenesis via upregulation of Dlk1-Dio3 locus miRNAs |
0027-8424 ; 1091-6490 |
Proceedings of the National Academy of Sciences |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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4596341 |
Guimaraes, Joao C.; Mittal, Nitish; Gnann, Alexandra; Jedlinski, Dominik; Riba, Andrea; Buczak, Katarzyna; Schmidt, Alexander; Zavolan, Mihaela |
A rare codon-based translational program of cell proliferation |
1474-7596 ; 1474-760X |
Genome Biology |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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4603336 |
Ghosh, Souvik; Guimaraes, Joao C.; Lanzafame, Manuela; Schmidt, Alexander; Syed, Afzal Pasha; Dimitriades, Beatrice; Börsch, Anastasiya; Ghosh, Shreemoyee; Mittal, Nitish; Montavon, Thomas; Correia, Ana Luisa; Danner, Johannes; Meister, Gunter; Terracciano, Luigi M.; Pfeffer, Sébastien; Piscuoglio, Salvatore; Zavolan, Mihaela |
Prevention of dsRNA-induced interferon signaling by AGO1x is linked to breast cancer cell proliferation |
0261-4189 ; 1460-2075 |
The EMBO Journal |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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4613851 |
Cléry, Antoine; Krepl, Miroslav; Nguyen, Cristina K. X.; Moursy, Ahmed; Jorjani, Hadi; Katsantoni, Maria; Okoniewski, Michal; Mittal, Nitish; Zavolan, Mihaela; Sponer, Jiri; Allain, Frédéric H.-T. |
Structure of SRSF1 RRM1 bound to RNA reveals an unexpected bimodal mode of interaction and explains its involvement in SMN1 exon7 splicing |
2041-1723 |
Nature Communications |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
|
4619192 |
Ghosh, Souvik; Börsch, Anastasiya; Ghosh, Shreemoyee; Zavolan, Mihaela |
The transcriptional landscape of a hepatoma cell line grown on scaffolds of extracellular matrix proteins |
1471-2164 |
BMC Genomics |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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4624863 |
Karousis, Evangelos D.; Gypas, Foivos; Zavolan, Mihaela; Mühlemann, Oliver |
Nanopore sequencing reveals endogenous NMD-targeted isoforms in human cells |
1474-7596 ; 1474-760X |
Genome Biology |
Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift) |
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Cooperations () |
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ID |
Kreditinhaber |
Kooperationspartner |
Institution |
Laufzeit - von |
Laufzeit - bis |
|
107594 |
Zavolan, Mihaela |
Stoffel, Markus, Group Leader |
ETH Zurich |
15.12.2007 |
31.12.2015 |
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2354647 |
Zavolan, Mihaela |
Allain, Frédéric |
ETH Zürich |
01.11.2011 |
30.04.2022 |
|
2834569 |
Zavolan, Mihaela |
Schümperli, Daniel, Prof |
University of Bern |
01.05.2014 |
30.04.2018 |
|
2834575 |
Zavolan, Mihaela |
Hall, Mike, Prof |
Biozentrum, University of Basel |
01.01.2010 |
31.12.2040 |
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2834582 |
Zavolan, Mihaela |
Mühlemann, Oliver, Prof |
Department of Chemistry and Biochemistry, Universität Bern |
01.05.2014 |
30.12.2025 |
|
2834643 |
Zavolan, Mihaela |
Grosshans, Helge, Group Leader |
Friedrich Miescher Institute |
01.05.2014 |
30.04.2018 |
|
2834648 |
Zavolan, Mihaela |
Polacek, Norbert, Prof |
Department of Chemistry and Biochemistry, Universität Bern |
01.05.2014 |
30.04.2018 |
|
3721911 |
Zavolan, Mihaela |
Spang, Anne |
Biozentrum, University of Basel |
01.05.2014 |
31.12.2040 |
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2354689 |
Zavolan, Mihaela |
Hall, Jonathan |
ETH Zürich |
01.11.2009 |
31.12.2035 |
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3721944 |
Zavolan, Mihaela |
Jeker, Lukas |
DBM, University Hospital Basel |
01.01.2015 |
31.12.2025 |
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4235374 |
Zavolan, Mihaela |
Ciaudo, Constance |
ETH Zürich |
01.05.2018 |
01.04.2020 |
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