Preface to the Second Edition

Ten years ago, Henri Buc enjoined us to view RNA polymerases as molecular motors, and to focus on understanding how the motor starts and runs, but also how it stops. The Royal Society of Chemistry volume which emerged from this perspective, ‘RNA Polymerases as Molecular Motors’, provided readers with a complete and detailed view of the key aspects of RNA polymerase structure and function, bringing together the perspectives of genetics, biochemistry, structural biology, biophysics, and modelling.

The absolutely central place of transcription in our contemporary understanding of biology cannot be underestimated, and this is true for both historical as well as conceptual reasons. From a historical standpoint, RNA polymerase is most probably the best-understood molecular system we have. The study of transcription has proceeded unabated since the earliest days of the molecular biological revolution, and a tremendous amount of fundamental knowledge has been obtained in this period which brings together numerous subfields of biology, but also has attracted the interest of numerous fields of science, including physics, chemistry, and mathematics. Whereas the fundamental study of other molecular systems has at times been waylaid by promises and dreams of translational applications and drug discovery, the study of RNA polymerase has remained predominantly fundamental, and the ongoing accumulation of this class of knowledge has permitted appropriate translational developments to emerge from the fundamental studies, rather than to push aside the fundamental studies. RNA polymerase stands out among molecular systems as one for which our knowledge is at its most advanced state. As a result, the ongoing discoveries made at the frontiers of this knowledge continue to irrigate all of the fields of biology.

Today we are pleased to provide you with the second installment of ‘RNA Polymerases as Molecular Motors’ which we hope will capture some of the exciting developments in our understanding of transcription over the last ten years. In essence we will take the motor for a ride around town to see how it deals with fuel shortages, traffic, and assorted obstacles it may typically encounter while on the road. The central premise of the book will be to explore how RNA polymerase carries out transcription in the crowded context of the cell. One of the main developments we hope to communicate is the increasingly broad yet detailed view of RNA polymerase as a central hub for the entire organism, integrating via unanticipated chemical and physical interactions a range of signals of the cellular state including metabolic capacity, cell cycle state, and DNA damage, to name but a few.

Because one of the likely reasons for the success of the first edition was its determination to synthesize and centralize a vast amount of mechanistically-relevant information that had been accumulated over the past decade or two, we felt it was vital that this new edition continue to fulfill this task as well. So as to keep the second edition fresh and lively, we proposed to rely on the first edition for the foundations of transcription – indeed the first edition, although out of print, remains a popular download on the Royal Society of Chemistry webstore. In this second edition we asked our contributors to update key established mechanistic developments, taking as granted the information already provided in the first edition. The book is thus organized in two parts; a first part which goes into the new workings of the motor that have recently been discovered, and a second part which focuses on how the RNAP motor integrates into the cellular landscape.

We hope you will enjoy your ride with this latest of models.

Robert Landick

Terence Strick

Jue Wang