Many flavors of biological diversity within RNA editing

RNA EditingEdited by Brenda L. BassOxford University Press, 2001. $110/£65 hbk (206 pages)ISBN 0 19 963815 2Before the articles contained in this or any other journal went to press, the spelling of every word was carefully scrutinized in a computer-assisted editing process, one of many levels for quality control. We take that for granted. But, until a scant 15 years ago, no-one thought that the ‘spelling’ of genetically encoded nucleotide sequences within some transcribed RNAs would also turn out to require one (or more) of many different kinds of editing process to create functional products. This departure from the outdated central dogma of molecular biology – DNA→RNA→protein – graced a 1986 issue of the journal Cell 1xMajor transcript of the frameshifted coxII gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA. Benne, R. et al. Cell. 1986; 46: 819–826Abstract | Full Text PDF | PubMed | Scopus (418)See all References1. To everyone's complete surprise, the paper showed that four uridylic acid residues are post-transcriptionally inserted into trypanosome pre-mRNAs encoding the coxII polypeptide of the cytochrome oxidase complex. In the absence of this ‘insertion RNA editing’, the RNA encoded a completely nonfunctional polypeptide.Before the end of the decade, examples of the fundamentally different ‘conversion editing’ were reported. The initial finding was in mammals: a C→U conversion introduces a stop codon in the pre-mRNA encoding apolipoprotein B, resulting in translation of a shortened form of the protein and thus affecting the intestinal absorption and transport of dietary lipid. Then, three different groups simultaneously found that in the mitochondria of higher plants C→U conversions in some pre-mRNAs result in different amino acid sequences than those specified by the genes. Subsequently, insertion RNA editing was reported where cytidylic acid residues are inserted into specific sites of certain myxomycete mitochondrial pre-mRNAs. Conversion RNA editing was described, in which A→I changes occur at specific pre-mRNA sites encoding some mammalian brain glutamate-gated ion-channel subunits; this editing facilitates fast synaptic neurotransmission. In mice altered experimentally so that these ion channels are not edited, the young animals go into progressively more and more violent convulsive seizures, leading to an early death.This new book on RNA editing brings together leading researchers to present eight review chapters – one couldn't ask for a more talented panel of authors. Given the great diversity of editing types, accomplished by numerous, fundamentally different molecular mechanisms, this book is designed so that each chapter can stand by itself. The authors have stressed completeness of literature coverage (I counted 741 references!) and, more importantly, timeliness. Every chapter covers the current status of the editing topic under consideration in great depth. For example, contrary to the original definition of editing as a post-transcriptional class of event, insertion editing in some Physarum mitochondrial and paramyxovirus P-gene transcripts is co-transcriptional. In the chapters on A→I conversion editing, we learn that not only does editing alter the coding capacity of some genes, but it can also be part of an autofeedback loop designed to regulate endogenous levels of an editing enzyme. There is simply no substitute for learning a subject from the people who work in the field, and the leading people at that. The words are enriched by numerous molecular figures that will aid the reader greatly in navigating what is an increasingly complex subject.It is conventional to place evolutionary discussions at the end of a series, and this is true in RNA Editing. However, I recommend that any reader of this book begin with the excellent final chapter in which Michael Gray discusses ‘speculations on the origin and evolution of editing’. Gray devotes considerable effort to reviewing briefly the various major diverse classes of RNA editing and their characteristics, before describing his thoughtful three-step model to explain the origin of RNA-editing systems and fitting it to several specific examples.I believe it is true to say that RNA editing does not yet enjoy the recognition it deserves, as I usually find it necessary to make a few descriptive comments to colleagues in other molecular biology-based fields when the topic comes up. This book will help not only to bring RNA editing into focus for the uninitiated, but also to provide a current status report for those already in the field and for the younger generation of biologists who are looking for an exciting new molecular discipline. As Brenda Bass very aptly states in the Preface, ‘RNA editing is a type of RNA processing which few scientists can afford to ignore.’