Philippe Jeanteur - Böcker

Epigenetics refers to heritable patterns of gene expression which do not depend on alterations of genomic DNA sequence. This book provides a state-of-the-art account of a few selected hot spots by scientists at the edge in this extremely active field. It puts special emphasis on two main streams of research. One is the role of post-translational modifications of proteins, mostly histones, on chromatin structure and accessibility. The other one deals with parental genomic imprinting, a process which allows to express a few selected genes from only one of the parental allele while extinguishing the other.

Splicing of primary RNA transcript, i.e. removal of introns and joining of exons to produce mature mRNAs competent for translation into proteins, is a quasi-systematic step of gene expression in higher organisms. However, this process is not unequivocal but can follow alternate pathways. Alternative splicing of a given transcript can therefore yield several distinct mRNAs encoding as many different proteins. Its full biological significance has not been appreciated until it was recognized that alternative splicing is so general as to affect about 75% of all human genes. Therefore, alternative splicing not only vastly increases protein diversity but also offers numerous opportunities for aberrant splicing events with pathological consequences.

The generality and quantitative extent of alternative splicing have only now begun to be fully appreciated. The first draft of the complete human genome led to the surprisingly low figure of about 32,000 genes. The extensive use of alternative splicing and its consequences in terms of coding capacity could account for this discrepancy and help fill the complexity gap between the genome and the proteome. After a computer-based assessment of the frequency of alternative splicing, this book addresses mechanistic aspects followed by examples of its involvement in important cellular processes. Finally, it raises the possibility of artificial modulation of alternative splicing by antisense nucleotides.

Animal cells present an extreme variability in their shapes in relation to their physiological properties. For instance, fibroblastic cells are tightly attached to the extra-cellular matrix and display a flattened, spindle-shaped morphology. Neuronal cells self-organize as a network through a complex branching of dendrites and a long axonal extension. Resting peripheral blood lymphocytes are poorly adhesive and maintain a spherical, smooth shape, while macroph- ages produce many pseudopodal extensions involved in the recognition of foreign molecules. In addition to the variability of the morphology of the cells that constitute different organs, many cell types also modify dynamically their morphology in response to environmental changes, leading to differential cell motility, migration, adhesion, polarity or intercellular contacts. This wide plasticity of cell morphology is promoted and maintained by the cytoskeleton, which is composed of the three interconnected actin micro filaments, tubulin microtubules and intermediate filaments networks, all capable of assembly and disassembly.Over the past few years, the Rho family of Ras-like GTPases emerged as key proteins that mediate extracellular signalling pathways leading to the forma- tion of polymerized actin-containing structures such as ruffles, lamellipodia and filopodia. Since the discovery of the first member RhoA in 1985, 13 mem- bers have so far been characterized in human cells. Most of Rho proteins are highly conserved between species as distant as yeast, slime mold, insects and mammals, which points to their fundamental role in cellular physiology.

Over the last few years remarkable progress has been accomplished with respect to our understanding of nuclear structure and trafficking. This volume concentrates on aspects that involve or are of relevance to RNA and RNPs. Topics include fundamental advances and current problems in the structural organization of different subnuclear compartments: chromatin, nucleolus and perinucleolar compartment, Cajal bodies and gems, speckles containing splicing factors, as well as the PML bodies characteristic of ProMyelocytic Leukemia. It also describes recent progress in the dynamic aspects of RNA trafficking and in the latest technologies for live cell imaging of mRNA. The major general message of this volume is that nuclear structure is much more dynamic than previously anticipated.

Epigenetics refers to heritable patterns of gene expression which do not depend on alterations of genomic DNA sequence. This book provides a state-of-the-art account of a few selected hot spots by scientists at the edge in this extremely active field. It puts special emphasis on two main streams of research. One is the role of post-translational modifications of proteins, mostly histones, on chromatin structure and accessibility. The other one deals with parental genomic imprinting, a process which allows to express a few selected genes from only one of the parental allele while extinguishing the other.

Splicing of primary RNA transcript, i.e. removal of introns and joining of exons to produce mature mRNAs competent for translation into proteins, is a quasi-systematic step of gene expression in higher organisms. However, this process is not unequivocal but can follow alternate pathways. Alternative splicing of a given transcript can therefore yield several distinct mRNAs encoding as many different proteins. Its full biological significance has not been appreciated until it was recognized that alternative splicing is so general as to affect about 75% of all human genes. Therefore, alternative splicing not only vastly increases protein diversity but also offers numerous opportunities for aberrant splicing events with pathological consequences.

The generality and quantitative extent of alternative splicing have only now begun to be fully appreciated. The first draft of the complete human genome led to the surprisingly low figure of about 32,000 genes. The extensive use of alternative splicing and its consequences in terms of coding capacity could account for this discrepancy and help fill the complexity gap between the genome and the proteome. After a computer-based assessment of the frequency of alternative splicing, this book addresses mechanistic aspects followed by examples of its involvement in important cellular processes. Finally, it raises the possibility of artificial modulation of alternative splicing by antisense nucleotides.

Animal cells present an extreme variability in their shapes in relation to their physiological properties. For instance, fibroblastic cells are tightly attached to the extra-cellular matrix and display a flattened, spindle-shaped morphology. Neuronal cells self-organize as a network through a complex branching of dendrites and a long axonal extension. Resting peripheral blood lymphocytes are poorly adhesive and maintain a spherical, smooth shape, while macroph- ages produce many pseudopodal extensions involved in the recognition of foreign molecules. In addition to the variability of the morphology of the cells that constitute different organs, many cell types also modify dynamically their morphology in response to environmental changes, leading to differential cell motility, migration, adhesion, polarity or intercellular contacts. This wide plasticity of cell morphology is promoted and maintained by the cytoskeleton, which is composed of the three interconnected actin micro filaments, tubulin microtubules and intermediate filaments networks, all capable of assembly and disassembly.Over the past few years, the Rho family of Ras-like GTPases emerged as key proteins that mediate extracellular signalling pathways leading to the forma- tion of polymerized actin-containing structures such as ruffles, lamellipodia and filopodia. Since the discovery of the first member RhoA in 1985, 13 mem- bers have so far been characterized in human cells. Most of Rho proteins are highly conserved between species as distant as yeast, slime mold, insects and mammals, which points to their fundamental role in cellular physiology.

Among all cellular RNA species of the three main types, ribosomal RNA, transfer RNA or messenger RNA, be they from prokaryotic or eukaryotic organisms, the prokaryotic mRNA is unique in that it has no precursor and is synthesized in the same mature form as it is translated into proteins. In fact, ribosomes join the nascent mRNA chain and engage in protein synthesis long before its transcription is complete. Provisions are even made for slowing down the ribo­ somes at some sites to prevent them from catching up with the RNA-polymerase. Of course, such a situation is only possible in the prokaryotic world where there is no such thing as a nuclear mem­ brane physically secluding the transcription process from the cy­ toplasm where translation is restricted. Quite in the opposite extreme, the eukaryotic pre-messenger RNA has to suffer many and sometimes drastic steps of maturation (capping, polyadenylation, splicing, edition) before the decision is made to export it to the cytoplasm. That is where it enters the scope of this book. Once in the cytoplasm, many options are still open to it: its entrance into polysomes may be delayed (as it is in unfertilized eggs) or merely prohibited (ferritin mRNA in iron-starved cells), directed to specific locations within the cytoplasm or be more or less rapidly degraded. During gametogenesis and early development, translational control is probably the most significant level of gene expression.

Biological functions are almost exclusively attributed to macromolecules, i.e. nucleic acids, proteins and polysaccharides. To gain their complete functional activities these biomolecules have to associate with the nuclear matrix, the cytoskeleton and the cell/plasma membranes. It is the aim of this series to discuss actual aspects in the field of structure-associated genetic and epigenetic functional processes. This series of survey reviews fills the gap in structure-associated information flow, and is a vital reference work for scientists in molecular and cell biology.