Structural Basis of Transciptional Pausing in Bacteria

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Date/Time:Wednesday, 30 Jan 2013 from 3:10 pm to 4:00 pm
Location:Hoover 1213
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Albert Weixlbaumer (The Rockefeller University)

Transcriptional pausing by multi-subunit RNA Polymerases (RNAPs) is a key mechanism for regulating gene expression in both prokaryotes and eukaryotes, and is a prerequisite for transcription termination. Pausing and termination states are thought to arise through a common, elemental pause state that is inhibitory for nucleotide addition. We report three crystal structures of Thermus RNAP elemental paused elongation complexes (ePECs). The structures reveal the same relaxed, open-clamp RNAP conformation in the ePEC that may arise by failure to reestablish DNA contacts during translocation. A kinked bridge-helix sterically blocks the RNAP active site, explaining how this conformation inhibits RNAP catalytic activity. Our results provide a framework for understanding how RNA hairpin formation stabilizes the paused state and how the ePEC intermediate facilitates termination.

I was born and raised in a small village in Austria. After finishing High School I started my undergraduate education at the University of Vienna where I studied Biology with the main focus on genetics and biochemistry. I did my master thesis in the lab of Prof. Renée Schroeder at the Institute of Microbiology and Genetics at the University of Vienna. I worked in collaboration with the bioinformatics group of Prof. Peter Schuster (also University of Vienna) as well as with Prof. Eric Westhof (IBMC Strasbourg, France) on the thermodynamics of RNA tertiary structure formation.

After receiving my Masters, I went to Cambridge, UK to work as a graduate student in the lab of Dr. Venki Ramakrishnan at the MRC - Laboratory of Molecular Biology at the University of Cambridge, UK. In the Ramakrishnan lab I studied several aspects of protein synthesis by X-ray crystallography including decoding by modified tRNAs, ribosome recycling and termination of translation.

After receiving my PhD in 2008, I moved to New York City to work with Prof. Seth A Darst. In the Darst lab I started a new project in the lab and studied transcriptional pausing by using biochemistry and X-ray crystallography.