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Basel, Switzerland

The Friedrich Miescher Institute for Biomedical Research is a world-class center for basic research in life science based in Basel, Switzerland. Wikipedia.

Fabian M.R.,McGill University | Sonenberg N.,McGill University | Filipowicz W.,Friedrich Miescher Institute for Biomedical Research
Annual Review of Biochemistry | Year: 2010

MicroRNAs (miRNAs) are small noncoding RNAs that extensively regulate gene expression in animals, plants, and protozoa. miRNAs function posttranscriptionally by usually base-pairing to the mRNA 3â€- untranslated regions to repress protein synthesis by mechanisms that are not fully understood. In this review, we describe principles of miRNA-mRNA interactions and proteins that interact with miRNAs and function in miRNA-mediated repression. We discuss the multiple, often contradictory, mechanisms that miRNAs have been reported to use, which cause translational repression and mRNA decay. We also address the issue of cellular localization of miRNA-mediated events and a role for RNA-binding proteins in activation or relief of miRNA repression. © 2010 by Annual Reviews. All rights reserved.

Schubeler D.,Friedrich Miescher Institute for Biomedical Research | Schubeler D.,University of Basel
Nature | Year: 2015

Cytosine methylation is a DNA modification generally associated with transcriptional silencing. Factors that regulate methylation have been linked to human disease, yet how they contribute to malignances remains largely unknown. Genomic maps of DNA methylation have revealed unexpected dynamics at gene regulatory regions, including active demethylation by TET proteins at binding sites for transcription factors. These observations indicate that the underlying DNA sequence largely accounts for local patterns of methylation. As a result, this mark is highly informative when studying gene regulation in normal and diseased cells, and it can potentially function as a biomarker. Although these findings challenge the view that methylation is generally instructive for gene silencing, several open questions remain, including how methylation is targeted and recognized and in what context it affects genome readout. © 2015 Macmillan Publishers Limited.

Padeken J.,Friedrich Miescher Institute for Biomedical Research | Heun P.,Max Planck Institute of Immunobiology and Epigenetics
Current Opinion in Cell Biology | Year: 2014

Heterochromatin was first defined by Emil Heitz in 1928 by light microscopy. In the 1950s electron microscopy studies revealed that heterochromatin preferentially localizes to the nuclear periphery and around the nucleolus. While the use of genomic approaches led to the genome wide identification of lamina-associated and nucleolus-associated chromatin domains (LADs, NADs), recent studies now shed light on the processes mediating this topology and its dynamics. The identification of different factors on all regulatory levels, such as transcription factors, histone modifications, chromatin proteins, DNA sequences and non-coding RNAs, suggests the involvement of multiple distinct tethering pathways. Positioning at these nuclear sub-compartments is often but not always associated with transcriptional silencing, underlining the importance of the pre-existing chromatin context. © 2014 Elsevier Ltd.

Schubeler D.,Friedrich Miescher Institute for Biomedical Research
Science | Year: 2012

Mammalian methylomes reveal how DNA methylation is infl uenced by the underlying nucleotide sequence.

Rass U.,Friedrich Miescher Institute for Biomedical Research
Chromosoma | Year: 2013

Genome duplication requires that replication forks track the entire length of every chromosome. When complications occur, homologous recombination-mediated repair supports replication fork movement and recovery. This leads to physical connections between the nascent sister chromatids in the form of Holliday junctions and other branched DNA intermediates. A key role in the removal of these recombination intermediates falls to structure-specific nucleases such as the Holliday junction resolvase RuvC in Escherichia coli. RuvC is also known to cut branched DNA intermediates that originate directly from blocked replication forks, targeting them for origin-independent replication restart. In eukaryotes, multiple structure-specific nucleases, including Mus81-Mms4/MUS81-EME1, Yen1/GEN1, and Slx1-Slx4/SLX1-SLX4 (FANCP) have been implicated in the resolution of branched DNA intermediates. It is becoming increasingly clear that, as a group, they reflect the dual function of RuvC in cleaving recombination intermediates and failing replication forks to assist the DNA replication process. © 2013 The Author(s).

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