The cytoplasmic fate of mRNA

Abstract

Translational Control of Gene Expression edited by N. Sonenberg, J. W. B. Hershey and M. B. Matthews Cold Spring Harbor Laboratory Press (2000) 1020 pages. ISBN 0–87969-568-4 US$115 At the beginning of the 90s most molecular biologists were focusing on transcription and RNA splicing. mRNA translation and its temporal and spatial regulation seemed research topics for insiders at that time. However, all aspects of mRNA fate in the cytoplasm will certainly attract much more attention during the next decade. The field is now flourishing with connections to all disciplines of biology. This book will help you to realize the tremendous variation of translational regulatory mechanisms existing in nature. The evidence for their importance has become so overwhelming that nobody seriously interested in gene expression can ignore it any longer. It is the great merit of the editors of this book that they have brought together an impressive series of first-class reviews written by the most prominent scientists in the field. The new monograph takes a fresh look at the field and is greatly expanded compared with the earlier 1996 version. The book is judiciously divided into two parts. The first part comprises eight broad chapters, giving an overview of the main principles of protein synthesis and its regulation. They serve as a thorough basis for the second part, which comprises twenty-eight chapters, each about 20 pages in length, that present in depth additional exciting areas in which there is strong research activity. Your appetite for this book will be stimulated right at the beginning by the wonderful introductory chapter, which is written jointly by the editors and defines the field in its entire complexity. Given that translation is of course a unifying principle of all living organisms, why are there such a large number of different control mechanisms modulating the use of mRNA templates and making actual protein level not predictable from RNA quantity alone? Are these just remnants of an RNA world or, as the authors seem to believe, effective adaptations for fine-tuning gene expression that have been opportunistically added during evolution? Five broad chapters are devoted to our knowledge of initiation, elongation and termination of translation both in eukaryotes and in prokaryotes. It is amazing how much detail has been added, in just the past five years, to our picture of the biochemistry, structure and function of ribosomes, initiation sites, and translation factors. However, translational control of gene expression is not just a matter of the translation machinery alone. It seems rather that the tremendously versatile mRNA sequences and structures impose the way they are seen by the translation apparatus and its factors. Particularly in eukaryotes, the untranslated parts of mRNAs play a decisive role by providing additional interaction sites for cytoplasmic proteins that modulate mRNA stability, mRNA localization or accessibility of mRNAs to translation. In turn, many of the proteins interacting with mRNA are themselves regulated by metabolites or post-translational modifications. This is beautifully documented in an exciting chapter on the role of translational control in developmental decisions. For example, in Drosophila, a specific cascade of factors acting on RNA localization and translation controls the anterior-posterior body axis. In C. elegans, the fate of germ-line cells is determined by translational repression. And you will find many more such examples. Another important section of the book is devoted to changes in translation that occur during virus infection. Again one is amazed by the variety of ways by which viruses divert the host translation apparatus for their own sake. The shorter chapters give insight into additional exciting areas in the field. For example, research into how heat shock or signal transduction pathways feed into translation, what we know about mRNA degradation of normal and nonsense-containing transcripts, and the evidence that local synaptic protein synthesis represents a molecular hallmark of learning and memory. This book is the most complete and up-to-date review of translational control mechanisms. It is a must for students entering the field, and it will constitute for many years a major reference guide for any investigator who is seriously interested in the full picture of gene expression.