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POL1PIC Report Summary

Project ID: 340964
Funded under: FP7-IDEAS-ERC
Country: Germany

Mid-Term Report Summary - POL1PIC (Dynamic architecture of the RNA polymerase I transcription initiation machinery)

Publishable brief summary of the achievements of the project
The summary should be a stand-alone description of the project and its outcomes. This text should be as concise as possible and suitable for dissemination to non-specialist audiences. Please notice that this summary will be published.
RNA polymerase (Pol) I and Pol III synthesize non-translated RNAs for ribosome assembly and protein synthesis, hence together they are accounting for almost 80% of the total transcriptional activity in growing yeast cells. Mis-regulation of Pol I and Pol III has been associated with several types of cancers. The POL1PIC project aims to elucidate the structure and dynamics of the Pol I transcription machinery in a broad and interdisciplinary approach. Since start of the POL1PIC complex, we have been able to determine the crystal structure of unbound Pol I at 3Å resolution and are currently determining high-resolution cryo-EM structures of Pol I bound to different transcription scaffolds. Comparison between unbound Pol I and elongating Pol I allows elucidating the conformational dynamic of the Pol I enzyme. These initial structures are currently followed up by the cryo-EM structure elucidation of the Pol I pre-initiation complex (PIC), where Pol I-specific general transcription factors are expressed and reconstituted with Pol I and Pol I-specific promoter DNA. Finally, we have established an integrative modeling workflow that allows using distance restraints from chemical crosslinking/mass spectrometry and automated modeling to generate models of multi-proteins assemblies. The method was initially tested using the 17-subunit Pol III and is currently applied to model the Pol I-PIC. Our results provide broad insight into the Pol I transcription machinery and are expected to greatly stimulate research on Pol I transcription related to human health.

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