Translational Control in Biology and Medicine

Edited by:
  • Michael B. Mathews,
  • Nahum Sonenberg &
  • John W. B. Hershey
Cold Spring Harbor Laboratory Press2007 • £75/$135

Translation control is staging a comeback, and the third edition of the Cold Spring Harbor Laboratory Press compendium on protein synthesis could not have come at a better time. Although regulation of protein synthesis has been studied extensively for over half a decade, the importance of this research has often not been appreciated by scientists outside the field. This sentiment is changing rapidly, and translational control is enjoying a renaissance following recognition of its role in crucial biological processes and human disorders. Even the evolution of the book's title mirrors the rise of this subject. The original (in 1996) was entitled simply Translational Control; the latest — Translation Control in Biology and Medicine — immediately suggests the progress in the field and hints at the focus of the book.

The 30 chapters of the book are written by experts in various niches of translation and cover an enormous breadth — from basic principles and building blocks of translational machinery to regulation of translation in distinct physiological states to the therapeutic opportunities that targeted intervention of translation offer. As the editors explain in the preface, the book embraces three main themes, which help the reader navigate through this almost 900-page tome. The first theme is the nuts and bolts of translation and its control. The contributors to this section review ribosome structure and function (of both prokaryotic and eukaryotic ribosomes), the mechanisms of initiation in various model systems (viral, yeast and mammalian) and physiological states (for example, signal transduction, cellular stress and apoptosis), and the cis-regulatory elements and trans-acting factors involved in the regulation of translation. The ribosome chapters are particularly enlightening as they provide a link between the high-definition structure of the ribosome and its function. They also present the ribosome as a dynamic machine rather than a static molecule. The reader is also given a historical view of the crucial discoveries that pushed the field forward and the progress that has been made. This will be especially appreciated by newcomers to this area because it puts into perspective many of the facts that we now take for granted.

The second theme is translation regulation in the biological processes at the forefront of current biomedical research. Protein synthesis is an intricate process that requires complicated cellular machinery as well as significant energetic commitment from the cell. It is not surprising that dysregulated translation is thought to underlie a number of human disorders. The chapters within this section describe our latest understanding of the involvement of translation in synaptic plasticity, memory and learning, embryonic development, metabolic disorders such as diabetes and obesity, development and progression of cancer, viral infection and mitochondrial dysfunction. In addition to providing mechanistic explanations of how translation and translational control play crucial parts in these disorders or disease states, it also offers a bench-to-bedside perspective on how these discoveries could be useful in developing therapeutic strategies. Specific examples are given of strategies to intervene with protein synthesis. For instance, promoting readthrough of nonsense mutations by small molecules results in amelioration of the clinical symptoms of several nonsense-mutation-mediated genetic disorders such as cystic fibrosis and Duchenne muscular dystrophy. Similarly, small molecules can change the frameshifting capacity of ribosomes, an attribute that is required by many viruses, including HIV, for infection.

The last theme provides an overview of new and rapidly growing areas of translation research. The chapters in this section review cellular IRES (internal ribosome entry site) elements, messenger RNA localization, microRNAs, translation in chloroplasts and riboswitches. Many of these concepts did not exist when the original book was published, and some of them are still controversial. The depth offered by the authors is considerable and offers the reader a glimpse of discoveries to come and a view of a research field that is evolving.

Sequels often suffer from several shortcomings, including the monotonous repetition of ideas and the absence of the most recent advances. Readers of previous versions might have expected only a modestly updated and expanded version this time. But they are in for a surprise: all of the chapters are either substantially rewritten or are completely new and contributed by new authors. This guarantees that the book is up to date and offers fresh ideas on the future of translation research. Given the scope of this book, even the editors themselves warn that few “will choose to read this volume from cover to cover, and certainly not in sequence.” I did, and I am glad. This book should not be missing from the shelves of any scholars of translation.