Protein Synthesis and the RNA World

In considering questions of the origins of life, many researchers have speculated that RNA was the earliest form of life, bridging the gap between a prebiotic era and the modern world of protein catalysts and DNA information storage. This suggestion initially came from the discovery of naturally occurring catalytic RNAs such as the Tetrahymena ribozyme and the RNA component of a tRNA processing enzyme known as RNase P. Even in extant systems, many enzyme cofactors have nucleotide or nucleotide-like components, such as ATP, NADH, and FAD. Furthermore, RNA both carries genetic information (mRNA) and performs catalysis (ribozymes).

If the “RNAworld” hypothesis is correct, what evidence is there that early protein synthesis mechanisms wereRNA controlled? First, there are three types of RNA that play major roles in translation—mRNA, which contains the genetic information; tRNA, the “adaptor” molecule; and rRNA, which comprises about 2/3 the mass of the ribosome. Mechanistically, some of the catalytic steps of protein synthesis have been mimicked using only RNA. Although several researchers have tried to demonstrate unequivocally that rRNA of modern organisms is the sole contributor of ribosomal function, the results are at best suggestive.However, the potential forRNA-catalyzed peptide bond formation is clear. In Darwinian-like experiments that select functional RNAs from large populations of partially randomized sequences, researchers have identified ribozymes that hydrolyze an aminoacyl ester, aminoacylate a tRNA, and form an amide bond between two amino acids. For example, such a selected ribozyme is able to catalyze formation of an amide bond between an AA–tRNA mimic and a peptidyl–tRNA mimic. Interestingly, this selected peptidyl transferase ribozyme contains some sequence and secondary structure elements of the region of E. coli 23S rRNA responsible for peptide bond formation.