“Regulatory RNAs”. Nikolaus Rajewsky

Using various ligation reactions, the Rajewsky’s lab identified thousands of miRNA-target interactions in vivo providing new insights in the specificity of miRNA target recognition. Moreover, they identified a novel lincRNA that is bound but not processed by Dicer, acting as a “Dicer sponge” in C.elegans. A part of its work is also focused on the elucidation of the function of circular RNAs that are not detected as linear molecules and that are also expressed in the brain.

Published data on circRNAs are annotated in www.circbase.org

“CEP63 deficiency promote p53 dependent microcephaly and reveals a role for the centrosome in meiotic recombination”. Travis H.Stracker

Mutations in human CEP63 centrosome protein cause Seckel syndrome, characterized by growth retardation and microencephaly. In mice deficient for CEP63, which recapitulate the human pathology, cell death seems to be due to the centrosome-based mitotic errors during brain development and microencephaly is completely rescued by p53 deletion.

“Widespread intron retention in mammals functionally tunes tanscriptomes”. Ulrich Braunschweig

Intron retention (IR) is the least well understood class of alternative splicing (AS) of precursor RNAs. Despite it represents the least prevalent form of AS in animals, it is quite frequent in mammals. It seems to be most frequent in poorly expressed genes and to affect genes with “inappropriate” functions, such as genes down-regulated in a given tissue. The results showed by Ulrich Braunschweig suggest that IR could act to reduce the level of transcripts that are less or not required within a specific cell or tissue.

“Nuclear ATP synthesis derived from ADP- ribose is essential for chromatin remodeling and hormonal gene regulation in breast cancer cells”. Roni H.G. Wright

In order to replicate DNA or to regulate gene expression, cells need a lot of energy, but how it is produced so fast in response to specific stimuli it is still unknown. The rapid gene expression modification and chromatin remodeling during an hormone response process represents a useful model in vitro to study fast production of energy within the cells. In breast cancer cells stimulated with progesterone, it is shown a rapid and transient accumulation of ATP in the nucleus in response to hormone due to the hydrolysis of poly-ADP-ribose to ADP-ribose. The inhibition of key enzymes that mediate the process results in chromatin remodeling underlying the important role of this enzymatic reaction in the gene regulation.

“Towards molecular systems biology of genome transcription”. Patrick Cramer

Cramer’s work aims to elucidate the mechanisms of genome transcription and its regulation in eukaryotic cells. Using structural biology methods and functional genomics, Cramer characterized the Pol II-mediator core initiation complex and the tail module that faces upstream DNA. Recent results described a cellular mechanism that buffers mRNA levels by compensating changes in mRNA synthesis and degradation and the discovery of the Xrn1 nuclease as a key enzyme in this homeostatic control. Finally, he gave a genome-wide description of specific termination of non coding-RNA synthesis that underlies transcriptome surveillance.