Regensburg 2016 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 28: Systems Biology & Gene Expression and Signalling

BP 28.5: Hauptvortrag

Dienstag, 8. März 2016, 11:15–11:45, H44

Molecular Bioimaging of Genome Transcription — •Patrick Cramer — Max Planck Institute for Biophysical Chemistry, Göttingen

Our laboratory studies the molecular mechanisms of eukaryotic gene transcription by integrated structural biology and elucidates the systemic principles of genome regulation with the use of funcitonal genomics and computational biology. Based on crystal structures of RNA polymerase II in different functional states we obtained a molecular movie of transcription (Cheung and Cramer, Cell 2012). With the use of functional genomics we elucidated how the transcription cycle is coordinated with co-transcriptional events (Mayer et al., Science 2012), and how a mechanism of transcriptome surveillance removes aberrant non-coding RNAs (Schulz, Schwalb et al., Cell 2013). Unexpected insights into transcription regulation came from the crystal structure of RNA polymerase I (Engel et al., Nature 2013). We have also used cryo-electron microscopy (cryo-EM) to resolve the architecture of an early Pol II elongation complex bound by the capping enzyme, which explains how capping occurs when the RNA first emerges from the Pol II surface (Martinez-Rucobo, Mol. Cell 2015). In my talk I will concentrate on our latest work where we combined different structural biology techniques to provide insights into the mechanism of gene regulation during transcription initiation, which requires the coactivator complex Mediator (Plaschka et al., Nature 2015). We reconstituted a recombinant, functional 15-subunit core of the Mediator complex and used cryo-EM and crosslinking to determine the architecture of the RNA polymerase II-Mediator core initiation complex. This work indicates how Mediator controls transcription and opens the way to the assembly and structural analysis of larger initiation complexes containing additional factors. I will present the latest unpublished work and demonstrate that cryo-EM enables us to obtain near-atomic resolution for large macromolecular assemblies, including mammalian RNA polymerase II.