RNA Silencing: With an Appendix on Gene Therapy Review

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(More customer reviews)The discovery of RNA interference in molecular biology has resulted in an explosion of interest in recent years. This interest is both academic and practical, and shows promise in drug discovery as well as in gene therapy and genetic engineering. This book gives essentially a literature survey of the latest research in RNA interference or RNA silencing as it is called in the book. Readers will need a substantial background in molecular biology to follow the contents, but anyone, including non-experts (such as this reviewer) can gain much from the book if it is read carefully and with attention paid to detail. Since it is a literature survey, readers will need ready access to the references that are quoted in the book.This reviewer only read the first six chapters so only these will be subject of the commentary here.

The author begins the book by an historical summary and then in chapter 2 begins discussing RNA silencing in plants. He points to three viewpoints for studying gene silencing by nucleotide sequences, namely the silencing of invading pathogens by viruses, the co-suppression of an inserted transgene, and homology-dependent gene silencing. The chapter emphasizes the first viewpoint, wherein small RNA sequences are used to defend against invading viruses. One example discussed is the use of mutated replicase of potato virus X (PVX) to induce resistance to the wild-type virus. Other examples include the correlation of virus resistance with post transcriptional suppression of transgene mRNA accumulation in tobacco etch virus and potato virus Y. Also interesting in this chapter is the discussion on the mobility of the post transcriptional gene silencing (PTGS) signal in plants.

The author takes a look at gene silencing in fungi in chapter 3, with emphasis on the role of repeat-induced point (RIP) mutations and `quelling'. The latter is a posttranscriptional mechanism that was discovered in Neurospora crassa. The quelling involved taking part of a gene involved in carotene synthesis and transforming the fungus with the result that the transgene caused the silencing of the endogenous gene.

The nematode C. elegans is one of the most widely studied organisms in functional genomics and molecular biology and so it is not surprising to see that RNA interference was investigated in it. The author discusses this research in chapter 4 of the book. The phenomenon of RNA interference is well supported in C. elegans as a reading of this chapter will reveal. One fascinating fact that is brought out by the author regarding C. elegans is that one half of its 600 somatic cells are neurons. The author reveals that partial resistance to RNA interference occurs in the nervous system of C. elegans, particularly in its head which had full resistance to RNA interference. He reports that some researchers have found techniques to circumvent this resistance.

Chapter 5 considers RNA silencing in insects, namely in Drosophila melanogaster and in mosquitoes. The molecular biology and genetics of Drosophila is of course well known, and the author discusses in fair detail RNA interference in this organism. The double stranded RNA that represents a certain gene in Drosophila can silence this gene and in fact is more efficient than single stranded RNA. The author includes a detailed model for RNA interference in Drosophila with accompanying diagrams. For mosquitoes, the author argues that an ideal situation would be one where the double stranded RNA is used successfully namely to suppress their own pathogens but also to abolish the replication of human viruses. He does not report too many of the details of research in RNA interference in mosquitoes. The genetic engineering of mosquitoes is very exciting via the possibility of releasing transgenic mosquitoes in the wild

In chapter 6 the author discusses RNA silencing in protozoa, and reports the surprising fact that it does not occur in some protozoa. In particular there is no RNA silencing in some Trypanosoma species and species in the genus Leishmania. The lack of RNA silencing in these organisms is a counterexample to the belief that RNA silencing evolved as a mechanism for the defense against retrotransposons, argues the author. For those eukaryotes that do not have RNA silencing, it thus becomes imperative to find the mechanisms they use for coping with transposons. The discussion of RNA silencing in Trypanosomatids is interesting also in that it points to the existence of the `kinetoplast', which is a unique organelle in the mitochondrion consisting of a large DNA network embedded in which they are minicircles and macrocircles. The minicircles apparently play a role in RNA editing. Also discussed and very interesting is the phenomenon of `transsplicing' in some protozoa, and wherein alternative exons can be spliced in the same pre-mRNA. This results in different mRNA as final product. The author gives a thorough discussion of transsplicing along with accompanying diagrams.

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Product Description:
This book focuses on an emerging, central issue in molecular genetics and the development of eukaryotes: the control of gene expression by small species of RNA. As an exciting new field of endeavor, it is the first book by a single author to deal comprehensively with RNA silencing.
The book provides the historical background of the field preceding the seminal work by Fire and associates in 1998 on the impact of small double-stranded RNA on the expression of nematode genes, which is considered the beginning of RNA silencing research. RNA silencing is described in a wide range of plants and animals including protozoa, simple metazoa, insects, non-mammalian vertebrates, and mammals. In each case the experimental results are provided with the accompanying background and with illustrations. There is also an appendix on the prospective use of RNA silencing in gene therapy, which is intended as a guide for investigators wishing to explore this possibility.