In recent years, unprecedented advances in many aspects of the molecular biology of nucleic acids have been witnessed. The area of RNA chemistry has undergone a kind of explosion, with a huge interest in RNA-mediated catalysis. At the same time, our structural understanding of DNA-protein interactions has increased enormously, and the related area of RNA-protein interactions is beginning to gather pace. This softcover edition from the successful series Nucleic Acids and Molecular Biology is devoted to the structure and mechanism of ribozymes, and their potential exploitation. The subject has both important evolutionary implications and potential practical application in the development of therapeutic agents for diseases such as AIDS.

Takes the reader through the origins of catalysis in RNA and necessarily includes significant discussion of structure and folding. The main focus of the book concerns chemical mechanism with extensive comment on how, despite the importance of RNA catalysis in the cell, its origins are still poorly understood and often controversial. The reader is given an outline of the important role of RNA catalysis in many aspects of cell function, including RNA processing and translation.

This special volume of Progress in Molecular Biology and Translational Science focuses on catalytic RNA. Written by experts in the field, the reviews cover a range of topics, from hammerhead ribozymes to spliceosome catalysis to Varkud satellite and hairpin ribozymes. Contributions from leading authorities Informs and updates on all the latest developments in the field

Behind the neologism “ribozymes” lies a family of fascinating molecules, ribo-enzymes, which have been relatively little studied. These catalytically active RNAs are found in all strata of life, from viruses to the human genome. At the end of the 1970s, the discovery of a catalytic RNA nestled in an intron, followed by another involved in the maturation of transfer RNAs, led to the discovery of new ribozymes and the transition from a strictly “proteocentric” vision, inherited from the dogma of molecular biology, to a more “nucleocentric” one. Since then, a variety of ribozymes have been identified in genomes, where their functions often remain mysterious. Looking at Ribozymes traces the discovery of these molecules and presents a picture of their functional diversity, catalytic mechanisms and distribution within the tree of life.

Ribozymes Provides comprehensive coverage of a core field in the molecular biosciences, bringing together decades of knowledge from the world’s top professionals in the field Timely and unique in its breadth of content, this all-encompassing and authoritative reference on ribozymes documents the great diversity of nucleic acid-based catalysis. It integrates the knowledge gained over the past 35 years in the field and features contributions from virtually every leading expert on the subject. Ribozymes is organized into six major parts. It starts by describing general principles and strategies of nucleic acid catalysis. It then introduces naturally occurring ribozymes and includes the search for new catalytic motifs or novel genomic locations of known motifs. Next, it covers the development and design of engineered ribozymes, before moving on to DNAzymes as a close relative of ribozymes. The next part examines the use of ribozymes for medicinal and environmental diagnostics, as well as for therapeutic tools. It finishes with a look at the tools and methods in ribozyme research, including the techniques and assays for structural and functional characterization of nucleic acid catalysts. The first reference to tie together all aspects of the multi-faceted field of ribozymes Features more than 30 comprehensive chapters in two volumes Covers the chemical principles of RNA catalysis; naturally occurring ribozymes, engineered ribozymes; DNAzymes; ribozymes as tools in diagnostics and therapy, and tools and methods to study ribozymes Includes first-hand accounts of concepts, techniques, and applications by a team of top international experts from leading academic institutions Dedicates half of its content to methods and practical applications, ranging from bioanalytical tools to medical diagnostics to therapeutics Ribozymes is an unmatched resource for all biochemists, biotechnologists, molecular biologists, and bioengineers interested in the topic.

The Discovery of Ribonuclease P and Enzymatic Activity of Its RNA Subunit Sydney Brenner and Francis H. C. Crick had a specific project in mind when they offered Sidney Altman a position in their group in 1969 to conduct postdoctoral research at the Medical Research Council Laboratory of Molecular Biology (LMB) in Cambridge, England. At the time, an intense international competition was on- ing in as many as a dozen labs to determine the three-dimensional structure of tRNA. At the LMB, Aaron Klug was attacking the structure by crystallographic analysis with Brian F. C. Clark providing large amounts of purified phenylalanine tRNA. (Eventually, Aaron announced his empirically determined 3-D structure of yeast phenylalanine tRNA, a structure that is generally common to tRNAs, due in part to several conserved, novel three-way nucleotide interactions. ) Concurrently, Michael Levitt, a Ph. D. student of Francis, was visually scrutinizing the cloverleaf secondary structure of the 14 tRNA sequences known at the time. Levitt was searching for nucleotide covariation in different parts of the molecules that were conserved in the 14 sequences known at the time. He identified a possible covariation of an apparent Watson-Crick pairing type between the residues at position 15 from the 5’ end of the tRNA and residue 48. This association implied these parts of the tRNA, namely the D loop containing residue 15 and the 5’ end of the T stem-adjoining residue 48, folded on one another in a tertiary structure shared by different tRNAs.

The discovery of ribozymes triggered a huge interest in the chemistry and biology of RNAs. Much of the recently made progress focusing on metal ions is addressed in Volume 9. This book, written by 28 internationally recognized experts, provides a most up-to-date view and it is thus of special relevance for colleagues teaching courses in biological inorganic chemistry and for researchers dealing, e.g., with nucleic acids, gene expression, and enzymology, but also for those in analytical and bioinorganic chemistry or biophysics. Structural and Catalytic Roles of Metal Ions in RNA describes metal ion-binding motives, methods to detect and characterize metal ion binding sites, and the role of metal ions in folding and catalysis. It deals with diffuse metal ion binding, RNA quadruplexes, the regulation of riboswitches, metal ions and ribozymes, including artificial ribozymes. The ribosome, ribozymes and redox cofactors, as well as the binding of kinetically inert metal ions to RNA are also considered.