Peptide bond formation catalyzed on the ribosome is a crucial event in the life on earth. The ribosome is a supercomplex of ribonucleoprotein particles containing both RNAs and proteins, and the peptide bond is produced on the peptidyl transferase center (PTC) of the large subunit of the ribosome. The high-resolution structures of the ribosome showed that the PTC is composed of only RNA. Although the ribosome seems to be a ribozyme, the foundation of the PTC and the evolutionary route of the ribosome are not clear. In this study, a possible evolutionary pathway for ribosome formation has been presented by combining a model experiment and the structural analysis of the ribosome. The current ribosome-catalyzed reaction could have evolved from a primitive system in the RNA world comprising proto-tRNA molecules like the minihelix. The missing link in the evolutionary route of the modern ribosome can be solved by considering tRNAs as primordial molecules comprising proto-ribosomes and proto-tRNAs, which form a symmetrical RNA dimer to constitute the PTC.

  Chiral-selective aminoacylation of an RNA minihelix (progenitor of the modern tRNA) could provide a crucial clue to solve the origin of homochirality in a biological system. In this reaction, an amino acid donor (aminoacyl phosphate oligonucleotide) is placed in close proximity to minihelix with the help of a bridging oligonucleotide, which possesses sequences complementary to both donor nucleotide and single-stranded NCCA of minihelix, to accomplish the chiral (L-amino acid)-selective aminoacylation of the minihelix. Here, we propose a molecular mechanism of chiral selectivity based on the mutational analysis of the donor and bridging nucleotides. The selectivity for L-amino acids is dependent on the stereochemistry of RNA. Due to cation coordination and sugar pucker, the side chain of D-amino acids is brought much closer to the terminal adenosine of the minihelix, thereby causing steric hindrance of the D-amino acids during amino acid transfer from the donor nucleotide to minihelix. This mechanism completely explains the result of the original chiral-selective aminoacylation experiment without any contradictions. This selective process may have determined the homochirality of L-amino acids in the putative RNA world.

This article is dedicated to the memory of Dr. Kaoru Harada.

　マジック20，すなわち20種のタンパク性アミノ酸がいかにして選ばれたかは，生命の起原研究にとって根元的な課題である．マジック20は精緻な選択を受けて選ばれたのではないと思われる．この問題の有効な研究法として，生命合成的な実験研究を提案する．