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RNA BIOLOGY

The RNA world ‘hypothesis’

Nature Reviews Molecular Cell Biology volume 23, page 582 (2022)Cite this article

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How has life emerged from scratch, and evolved to current living systems? This question has always intrigued us. The RNA world hypothesis — which postulates that RNA with both genetic information and catalytic activity had an essential role in the origin of life — is now supported by many scientists. Two seminal papers published in the early 1990s investigated this hypothesis using different approaches.

In June 1992, Harry F. Noller and colleagues reported an interesting biochemical (reductive) approach that demonstrated the involvement of 23S ribosomal RNA (rRNA) in peptidyl transferase (PTase) activity. The authors removed ribosomal proteins from 50S ribosomal subunits of Thermus aquaticus without disturbing the structure of rRNA and on this preparation performed a fragment reaction, which mimics peptidyl transfer from peptidyl-tRNA to an aminoacyl-tRNA analogue. Surprisingly, the ribosomal subunits maintained their PTase activity, even after 95% of the ribosomal proteins were removed. Their results strongly indicated that 23S rRNA is a ribozyme (RNA enzyme) that catalyses peptide bond formation, but their statement was modest to say that “Direct proof for the hypothesis that peptide bond formation is catalyzed solely by rRNA will require demonstration of activity with completely protein-free preparations.” The precise X-ray structure of the 50S ribosome was only solved in 2000, in which no visible peptide chain within 18 Å from the PTase centre was observed, providing the structural evidence that 23S rRNA catalyses peptide bond formation.

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References

Original articles

  • Noller, H. F. et al. Unusual resistance of peptidyl transferase to protein extraction procedures. Science 256, 1416–1419 (1992)

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  • Bartel, D. P. & Szostak, J. W. Isolation of new ribozymes from a large pool of random sequences. Science 261, 1411–1418 (1993)

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  1. Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan

    Hirohide Saito

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  1. Hirohide Saito
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Correspondence to Hirohide Saito.

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Saito, H. The RNA world ‘hypothesis’. Nat Rev Mol Cell Biol 23, 582 (2022). https://doi.org/10.1038/s41580-022-00514-6

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