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To thrive, every living cell must continuously gauge and respond to
changes in its environment. These changes are ultimately
implemented by modulating gene expression, a process that relies on
transcription by Nature's most multivalent molecular machine, the
RNA polymerase. This book covers progress made over the past decade
understanding how this machine functions to compute the cellular
state, from the atomistic structural level responsible for
chemistry to the integrative level at which RNA polymerase
interacts with the other key molecular machineries of the cell.
The cell can be viewed as a 'collection of protein machines' and
understanding these molecular machines requires sophisticated
cooperation between cell biologists, geneticists, enzymologists,
crystallographers, chemists and physicists. To observe these
machines in action, researchers have developed entirely new
methodologies for the detection and the nanomanipulation of single
molecules. This book, written by expert scientists in the field,
analyses how these diverse fields of research interact on a
specific example - RNA polymerase. The book concentrates on RNA
polymerases because they play a central role among all the other
machines operating in the cell and are the target of a wide range
of regulatory mechanisms. They have also been the subject of
spectacular advances in their structural understanding in recent
years, as testified by the attribution of the Nobel prize in
chemistry in 2006 to Roger Kornberg. The book focuses on two
aspects of the transcription cycle that have been more intensively
studied thanks to this increased scientific cooperation - the
recognition of the promoter by the enzyme, and the achievement of
consecutive translocation steps during elongation of the RNA
product. Each of these two topics is introduced by an overview, and
is then presented by worldwide experts in the field, taking the
viewpoint of their speciality. The overview chapters focus on the
mechanism-structure interface and the structure-machine interface
while the individual chapters within each section concentrate more
specifically on particular processes-kinetic analysis,
single-molecule spectroscopy, and termination of transcription,
amongst others. Specific attention has been paid to the newcomers
in the field, with careful descriptions of new emerging techniques
and the constitution of an atlas of three-dimensional pictures of
the enzymes involved. For more than thirty years, the study of RNA
polymerases has benefited from intense cooperation between the
scientific partners involved in the various fields listed above. It
is hoped that a collection of essays from outstanding scientists on
this subject will catalyse the convergence of scientific efforts in
this field, as well as contribute to better teaching at advanced
levels in Universities.
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