Ribozyme-Catalyzed Genetics

Abstract

RNA World research in recent years has sought to establish whether ribozymes have the catalytic versatility and potency to transmit genetic information and to sustain a credible metabolism. At a minimum, organisms from just before the Protein Revolution would have had to catalyze nucleotide polymerization and invent the machinery for protein synthesis. There are now RNA enzymes (ribozymes) that catalyze the individual steps in each of these reactions. Some of the current challenges include increasing the vigor with which the individual reactions are catalyzed, strengthening the affinity and specificity of substrate recognition, integrating ribozymes into metabolic paths and coordinated networks of linked reactions, and deriving a ribozyme-catalyzed metabolic context to sustain the core reactions. RNA World theories of the earliest evolution of life enjoy increasing acceptance and experimental support. The simplest statement of the RNA World theory is that our evolutionary history includes at least one organism that depended on RNA molecules both as the primary repository for genetic information and as the principle set of catalysts for cellular functions. In modern organisms, these two roles are predominantly filled by DNA and proteins, respectively. RNA World organisms are variously referred to as "ribo-organisms" or "ribocytes." The first ribocyte to make use of genetically encoded translation is called the "breakthrough organism." Far removed both from life's origins and from recognizably modern biochemistry, the descendents of the breakthrough organism are thought to have accumulated a broad diversity of proteins enzymes that took over nearly all of the functions of the cell. The transition from ribocytes to modern forms may have left traces of the ancestral state in the form of nucleotide cofactors, ribosomes built largely from RNA, and the requirement for ribonucleotides as biosynthetic precursors for deoxyribonucleotides. Speculation on how this transition may have taken place, and the relevant experimental evidence, are discussed in other chapters of this volume. This review evaluates the degree to which ribozymes identified to date are adequate to the task of sustaining genetic information flow. Emphasis is on the reactions that underlie transmission of genetic information. The first section defines the aspects of RNA World theories that are within the purview of this endeavor. The next two sections describe the evolution, activities, and experimental challenges of ribozymes that catalyze each of the discrete reactions of replication and proteins synthesis. The fourth section addresses progress towards generating an RNA-catalyzed metabolism to support the flow of genetic information, and the fifth section offers concluding remarks. Additional reviews in related areas have been published elsewhere. 1,5-9