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MicroRNAs (miRNAs) are RNA molecules, conserved by evolution, that regulate gene expressions and their discovery has revolutionised both basic biomedical research and drug discovery. Expression levels of miRNAs have been found to vary between tissues and with developmental stages and hence evaluation of the global expression of miRNAs potentially provides opportunities to identify regulatory points for many different biological processes. This wide-ranging reference work, written by leading experts from both academia and industry, will be an invaluable resource for all those wishing to use miRNA techniques in their own research, from graduate students, post-docs and researchers in academia to those working in R&D in biotechnology and pharmaceutical companies who need to understand this emerging technology. From the discovery of miRNAs and their functions to their detection and role in disease biology, this volume uniquely integrates the basic science with industry application towards drug validation, diagnostic and therapeutic development.
MicroRNA research is enjoying an inflationary period of astonishingly rapid progress that began in 2001 after a relatively long gestation. The idea that small RNAs could regulate gene expression by base-pairing to messenger RNAs can be traced back more than 45 years. In a 1961 Journal of Molecular Biology paper, Jacob and Monod proposed an antisense RNA base-pairing model for the lac repressor/operator interaction that they had defined genetically. The lac repressor turned out to be a protein, but the field of antisense RNA mediated gene regulation grew steadily through studies of authentic antisense regulatory RNAs in bacteria. The identification in 1993 of the lin-4 microRNA and its antisense regulation of lin-14 did not trigger a surge of interest in antisense gene regulation in eukaryotes, primarily because lin-4 did not exhibit any evident conservation outside nematodes (although we now know that lin-4 is related to vertebrate mir-125, but is not close enough to be detected by the methods available in the era before the availability of genome sequences). Even the identification in 2000 of let-7, a second microRNA in C. elegans, did not immediately stimulate a sense among biologists that these exceptionally small RNAs could represent a general phenomenon. I must admit that I was among the skeptical majority.
The modern era of microRNA biology began with the finding from the Ruvkun laboratory, reported in a 2000 Nature paper, that the let-7 microRNA has been conserved almost precisely in all its 21 nt for more than 400 million years: since the common ancestor of all bilaterally symmetric animals.
Twenty-five years ago it was possible to predict that many more RNAs that were known at that time would be found: Some of them would be catalytic and some of them would not be but would serve other functions. The prediction turned out to be spectacularly true and this book deals with one class of novel RNAs, the microRNAs (miRNAs). The task now is to elucidate the nature and function of all these new RNAs.
This book is a compendium of experimental methods, in silico and the traditional kind, of analyzing the miRNAs. There are many chapters on miRNAs on intra-cellular functions, in developmental events and in disease. A newcomer would do well to have this volume handy for purposes of reference and for its educational value per se. There are not many books on miRNAs that have such an extensive and complete view of the field as it now exists. My hope is that the problems presented here will be worked on assiduously to pave the way for a new synthesis of various RNAs as important regulatory genes in eukaryotes.