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NCCR RNA & Disease
Third-party funded project
Project title NCCR RNA & Disease
Principal Investigator(s) Zavolan, Mihaela
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
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

Published results ()

  ID Autor(en) Titel ISSN / ISBN Erschienen in Art der Publikation
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) 
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) 
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) 
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) 
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) 
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) 
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) 
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) 

Cooperations ()

  ID Kreditinhaber Kooperationspartner Institution Laufzeit - von Laufzeit - bis
107594  Zavolan, Mihaela  Stoffel, Markus, Group Leader  ETH Zurich  15.12.2007  31.12.2015 
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 
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 
2354689  Zavolan, Mihaela  Hall, Jonathan  ETH Zürich  01.11.2009  31.12.2035 
3721944  Zavolan, Mihaela  Jeker, Lukas  DBM, University Hospital Basel  01.01.2015  31.12.2025 
4235374  Zavolan, Mihaela  Ciaudo, Constance  ETH Zürich  01.05.2018  01.04.2020 
   

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