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RNA, the Epicenter of Genetic Information

RNA, the Epicenter of Genetic Information

by John Mattick, Paulo Amaral
RNA, the Epicenter of Genetic Information

RNA, the Epicenter of Genetic Information

by John Mattick, Paulo Amaral

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Overview

The origin story and emergence of molecular biology is muddled. The early triumphs in bacterial genetics and the complexity of animal and plant genomes complicate an intricate history. This book documents the many advances, as well as the prejudices and founder fallacies. It highlights the premature relegation of RNA to simply an intermediate between gene and protein, the underestimation of the amount of information required to program the development of multicellular organisms, and the dawning realization that RNA is the cornerstone of cell biology, development, brain function and probably evolution itself. Key personalities, their hubris as well as prescient predictions are richly illustrated with quotes, archival material, photographs, diagrams and references to bring the people, ideas and discoveries to life, from the conceptual cradles of molecular biology to the current revolution in the understanding of genetic information.

Key Features

  • Documents the confused early history of DNA, RNA and proteins - a transformative history of molecular biology like no other.
  • Integrates the influences of biochemistry and genetics on the landscape of molecular biology.
  • Chronicles the important discoveries, preconceptions and misconceptions that retarded or misdirected progress.
  • Highlights major pioneers and contributors to molecular biology, with a focus on RNA and noncoding DNA.
  • Summarizes the mounting evidence for the central roles of non-protein-coding RNA in cell and developmental biology.
  • Provides a thought-provoking retrospective and forward-looking perspective for advanced students and professional researchers.


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Product Details

ISBN-13: 9781000623116
Publisher: CRC Press
Publication date: 09/20/2022
Sold by: Barnes & Noble
Format: NOOK Book
Pages: 404
Sales rank: 787,361

About the Author

John Mattick is the Professor of RNA Biology at UNSW Sydney. He obtained his PhD in Biochemistry at Monash University in Melbourne and undertook his postdoctoral training at Baylor College of Medicine in Houston. Most recently he was the Chief Executive of Genomics England, Executive Director of the Garvan Institute of Medical Research in Sydney, and Director of the Institute for Molecular Bioscience, the Australian Genome Research Facility, the ARC Special Research Centre for Molecular and Cell Biology, and the ARC Special Research Centre for Functional and Applied Genomics at the University of Queensland.

His research interests have been focused for the past three decades on the role of regulatory RNAs in the evolution and development of complex organisms. He pioneered the thesis that the majority of the genome of humans and other complex organisms, previously considered to be ‘junk’, is devoted to regulatory RNAs that direct the epigenetic trajectories of differentiation and development. He has published over 300 research articles and reviews, which have been cited over 83,000 times. His work has received editorial coverage in Nature, Science, Scientific American, New Scientist and the New York Times. It has also been highlighted in two books: The Deeper Genome by John Parrington and Promoting the Planck Club by Don Braben.

He has received numerous awards including the International Union of Biochemistry and Molecular Biology Medal, the University of Texas MD Anderson Cancer Center Bertner Award for Distinguished Contributions to Cancer Research, and the Human Genome Organization Chen Medal for Distinguished Achievement in Human Genetics and Genomic Research. He is a Fellow of the Australian Academy of Science, the Royal Society of New South Wales, the Australian Academy of Technology and Engineering and the Australian Academy of Health and Medical Sciences. He is also an Associate Member of the European Molecular Biology Organization.

Paulo Amaral is an Assistant Professor of Bioengineering at Insper in São Paulo, Brazil. He obtained his MSc in Biochemistry at the Institute of Chemistry, University of São Paulo, and PhD in Molecular Genetics at the Institute for Molecular Bioscience, University of Queensland, in Brisbane. He undertook his postdoctoral training at the CRUK/Wellcome Trust Gurdon Institute and Milner Therapeutics Institute, University of Cambridge, supported by a Royal Society and British Academy Newton International Fellowship, Corpus Christi College Research Fellowship and Borysiewicz Biomedical Sciences Fellowship.

He has also taught at different institutions as visiting lecturer at both undergraduate and graduate levels, including at the Karolinska Institutet and Uppsala University in Sweden, and Humanitas University and Università Campus Bio-Medico di Roma in Italy. Since 2004, his research has explored the roles of noncoding DNA, regulatory RNAs and RNA modifications in a variety of biological systems, in both academia and industry. He was one of the first to show that noncoding RNAs associate with chromatin and guide chromatin modifications for gene activation, and has been a longstanding student of the history of molecular biology, especially of the overlooked middleman, but almost certainly the key player, RNA.

Table of Contents


Preface


Chapter 1 Overview
• The genetic material?
• Halcyon days
• Worlds apart
• Huge genomes, strange genetics
• The age of Aquarius
• All that junk
• The expanding repertoire of RNA
• Glimpses of a modern RNA world
• Genome sequencing and transposable elements
• The human genome
• Small RNAs with mighty functions
• Large RNAs with many functions
• The epigenome
• The programming of development
• RNA and repeats rule
• Plasticity
• Beyond the jungle of dogmas


Chapter 2 The genetic material?
• The nature of matter
• Sugars and fats
• Proteins: ‘the locus of life’
• Nucleic acids and chromosomes
• Chromosomes as the mediators of genetic inheritance
• The ‘Modern Synthesis’
• Distinguishing DNA and RNA
• One gene-one protein and the ‘nature of mutations’
• DNA is the genetic material
• The double helix – icon of the coming age


Chapter 3 Halcyon days
• The big question
• Discovery of the ribosome
• The messenger and the adaptor
• The ‘genetic code’
• The lac operon and gene regulation
• Protein structure
• The Central Dogma
• It’s all over now


Chapter 4 Worlds apart
• The origin of cells
• Genetic recombination
• The emergence of complex organisms
• Chromatin
• Chromatin-associated RNA
• Early models of RNAs in nuclear architecture
• Heterogenous nuclear RNA
• Heroes or fools?


Chapter 5 Strange genomes, strange genetics
• Repetitive DNA
• Controlling elements
• Paramutation, imprinting and transinduction
• The bithorax ‘complex locus'
• Transvection
• Epigenetic modifiers
• The Britten and Davidson model
• Boolean models of combinatorial control
• Processed RNAs as global regulators
• Out on a limb


Chapter 6 The Age of Aquarius
• Recombinant DNA and ‘gene cloning’
• Enabling technologies
• DNA sequencing
• The gold rushes
• Hox genes
• Oncogenes and tumor suppressors
• Immunology and monoclonal antibodies
• Biotechnological exploitation
• Cell-free DNA amplification and shotgun cloning
• A world of proteins


Chapter 7 All that junk
• The C-value enigma
• Duplication and transposition
• Mutational load, nonsense DNA, nonsense RNA
• Neutral evolution
• Conservation and selection
• Junk DNA
• Selfish DNA
• Genes-in-pieces!
• Not junk?


Chapter 8 The expanding repertoire of RNA
• Spliceosomal RNAs
• Small nucleolar RNAs
• Other small guide, scaffolding and regulatory RNAs
• Catalytic RNAs and the ancient RNA World hypothesis
• The catalytic heart of splicing and translation
• The digital and analog faces of RNA
• Candles in the dark


Chapter 9 Glimpses of a modern RNA world
• Riboregulators
• Riboswitches
• Antisense RNAs and complex transcription in eukaryotes
• Long untranslated RNAs
• UTR derived RNAs
• First glimpses of small regulatory RNAs in animals
• Curiosities or emissaries?


Chapter 10 Genome sequences and transposable elements
• Genome mapping
• Genetics at genome scale
• Whole genome sequencing of bacteria and archaea
• Genome sequencing of unicellular eukaryotes
• Genome sequencing of model plants and animals
• The G-value enigma
• Comparative genomics at nucleotide resolution
• Pseudogenes and retrogenes
• Transposable elements as functional modules
• Transposable elements as drivers of phenotypic innovation
• The great exploration – the diversity of life
• From genome sequence to genome biology


Chapter 11 The human genome
• The project
• Assessment of functionality
• The majority of the genome is active
• Damaged genes
• A plethora of ‘rare’ diseases
• Complex traits and disorders
• The transformation of medical research and healthcare


Chapter 12 Small RNAs with mighty functions
• Unusual genetic phenomena involving RNA
• The RNA interference pathway
• Transcriptional gene silencing: RNA-directed DNA methylation
• Research and biotechnology applications
• MicroRNAs
• Piwi-associated RNAs (piRNAs)
• Other classes of small RNAs
• RNA communication between species
• CRISPR
• RNA-directed genome editing


Chapter 13 Large RNAs with many functions
• Pervasive transcription
• The amazing complexity of the transcriptome
• Protein-coding or noise?
• The restricted expression of long noncoding RNAs
• Other indices of functionality of long noncoding RNAs
• The genetic signatures of long noncoding RNAs
• An avalanche of long noncoding RNAs
• A plethora of functions
• The Wild West


Chapter 14 The epigenome
• Chromatin structure
• Topological domains
• Enhancers
• Nucleosomes and histones
• Nucleosome remodeling
• Histone modifications
• The histone code
• DNA methylation
• The regulation of development


Chapter 15 The programming of development
• Autopoiesis
• The overarching question
• Tissue architecture and cell identity
• Programmed ontogeny
• Lineage specification
• How much information is required?
• Constraints imposed by the superlinear scaling of regulatory information
• How much information is there in the human genome?
• Genomes as .zip files of transcriptomes


Chapter 16 RNA and repeats rule
• RNA is a core component of chromatin
• Regulation of chromosome structure
• RNA guidance of chromatin remodeling
• Guidance of transcription factors
• Guidance of DNA methylation
• Guidance of histone modifications
• Xist as the exemplar
• Enhancer RNAs and chromatin structure
• RNA scaffolding of phase-separated domains
• An addition to the ancient RNA world hypothesis
• Structure-function relationships in lncRNAs
• A new view of the genome of complex organisms


Chapter 17 Plasticity
• RNA modifications and the unknown epitranscriptome
• The expansion of RNA editing in cognitive evolution
• A>I editing
• C>U editing
• The brain
• RNA-directed transgenerational epigenetic inheritance


Chapter 18 Beyond the jungle of dogmas
• The misunderstanding of molecular biology
• The evolution of evolvability


References

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