The molecular basis of Eukaryotic Transcription

Lecture lecture G16 is now full for this lecture. However, tickets are available to watch the lecture streamed live in Lecture Theatre G34. Please email l.brown@imperial.ac.uk including a postal address.

Professor Roger Kornberg, Professor in Medicine at Stanford University and winner of the 2006 Nobel Prize in Chemistry presents the Schrodinger Lecture 2008.

Abstract: A complete RNA polymerase II transcription system has been derived by the fractionation of yeast and mammalian cell extracts.  The required polypeptides comprise the 12-subunit RNA polymerase II, multiple “general transcription factors”, and a 20-subunit “Mediator”.  The general transcription factors are responsible for promoter recognition and for melting the DNA template for the initiation of transcription.  Mediator makes the key connection between enhancers and promoters.  It transduces regulatory information from activator and repressor proteins to RNA polymerase II. 

Structural studies of the RNA polymerase II transcription machinery began with electron microscope analysis of two-dimensional protein crystals formed on lipid layers.  This led to the derivation of a 10-subunit form of RNA polymerase II especially conducive to crystallization, and to the use of two-dimensional crystals as seeds for the growth of large single crystals for X-ray analysis.  The large size of the polymerase, over half a million Daltons, presented unusual technical difficulties, eventually overcome, and the structure was determined at 2.8 Angstroms resolution.

RNA polymerase II was also crystallized in the form of an actively transcribing complex, containing template DNA and product RNA.  The structure of this complex was solved by molecular replacement, revealing the DNA entering and unwinding in the active center cleft.  Nine base pairs of DNA-RNA hybrid could be seen extending from the active center at nearly right angles to the entering DNA.  Protein-nucleic acid contacts help explain the specificity of RNA synthesis, RNA and DNA translocation during transcription elongation, and DNA and RNA strand separation for product release.

RNA polymerase II crystallography has been extended to general transcription factors.  The results have been assembled in a preliminary picture of a complete transcription initiation complex.  From this picture, principles of both the initiation of transcription and its regulation may be derived.
Biography:  Roger Kornberg is Winzer Professor in Medicine in the Department of Structural Biology at Stanford University. In his doctoral research, he demonstrated the diffusional motions of lipids in membranes, termed flip-flop and lateral diffusion. He was a postdoctoral fellow and member of the scientific staff at the Laboratory of Molecular biology in Cambridge, England from 1972-5, where he discovered the nucleosome, the basic unit of DNA coiling in chromosomes. He moved to his present position in 1978, where his research has focused on the mechanism and regulation of eukaryotic gene transcription.

Notable findings include the demonstration of the role of nucleosomes in transcriptional regulation, the establishment of a yeast RNA polymerase II transcription system and the isolation of all the proteins involved, the discovery of the Mediator of transcriptional regulation, the development of two-dimensional protein crystallization and its application to transcription proteins, and the atomic structure determination of an RNA polymerase II transcribing complex.

Kornberg was elected to the National Academy of Sciences in 1993. He has received many awards, including the 2001 Welch prize, highest award in chemistry in the United States, the 2002 Leopold Mayer Prize, highest award in biomedical sciences of the French Academy of Sciences, and the 2006 Nobel Prize in Chemistry (unshared). 

Kornberg’s closest collaborator has been his wife, Dr. Yahli Lorch. They have three children, Guy, Maya, and Gil.

A drinks reception will follow the lecture.

Ticket: Registration in advance