Thomas R. Cech
Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309-0215 Correspondence: email@example.com
There are two RNAworlds. The ﬁrst is the primordial RNAworld, a hypothetical era when RNA served as both information and function, both genotype and phenotype. The second RNA world is that of today’s biological systems, where RNA plays active roles in catalyzing biochemical reactions, in translating mRNA into proteins, in regulating gene expression, and in the constant battle between infectious agents trying to subvert host defense systems and host cells protecting themselves from infection. This second RNA world is not at all hypothetical, and although we do not have all the answers about how it works, we have the tools to continue our interrogation of this world and reﬁne our understanding. The fun comes when we try to use our secure knowledge of the modern RNAworld to infer what the primordial RNAworld might have looked like.
1 The primordial RNA world 2 The contemporary RNA world 3 The world of RNA technology and medical applications References
Editors: John F. Atkins, Raymond F. Gesteland, and Thomas R. Cech Additional Perspectives on RNA Worlds available at www.cshperspectives.org Copyright # 2012 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a006742 Cite as Cold Spring Harb Perspect Biol 2012;4:a006742
1 THE PRIMORDIAL RNA WORLD The term “RNA world” was ﬁrst coined by Gilbert (1986), who was mainly interested in how catalytic RNA might have given rise to the exon–intron structure of genes. But the concept of RNA as a primordial molecule is older, hypothesized by Crick (1968), Orgel (1968), and Woese (1967). Noller subsequently provided evidence that ribosomal RNA is more important than ribosomal proteins for the function of the ribosome, giving experimental support to these earlier speculations (Noller and Chaires 1972; Noller 1993). The discovery of RNA catalysis (Kruger et al. 1982; Guerrier-Takada et al. 1983) provided a much ﬁrmer basis for the plausibility of an RNA world, and speculation was rekindled. The ability to ﬁnd a broad range of RNA catalysts by selection of RNAs from large random-sequence libraries (SELEX) (Ellington and Szostak 1990; Tuerk and Gold 1990; Wright and Joyce 1997) fueled the enthusiasm, and made it possible to conceive of a ribo-organism that carried out complex metabolism (Benner et al. 1989). The widely accepted order of events for the evolution of an RNA world and from the RNA world to contemporary biology is summarized in Figure 1. Did an RNA world exist? Some of the most persuasive arguments in favor of an RNA world are as follows. First, RNA is both an informational molecule and a biocatalyst—both genotype and phenotype—whereas protein has extremely limited ability to transmit information (as with prions). Thus, RNA should be capable of replicating
Complex organic molecules produced by random chemistry
RNA World Time
Figure 1. An RNAworld model for the successive appearance of RNA,
proteins, and DNA during the evolution of life on Earth. Many isolated mixtures of complex organic molecules failed to achieve selfreplication, and therefore died out (indicated by the arrows leading to extinction.) The pathway that led to self-replicating RNA has been preserved in its modern descendants. Multiple arrows to the left of self-replicating RNA cover the likely self-replicating systems that preceded RNA. Proteins large enough to self-fold and have useful activities came about only after RNAwas available to catalyze peptide ligation or amino acid polymerization, although amino acids and short peptides were present in the mixtures at far left. DNA took over the role of genome more recently, although still .1 billion years ago. LUCA (Last Universal...