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Simple peptides derived from the ribosomal core potentiate RNA polymerase ribozyme function

Abstract

The emergence of functional interactions between nucleic acids and polypeptides was a key transition in the origin of life and remains at the heart of all biology. However, how and why simple non-coded peptides could have become critical for RNA function is unclear. Here, we show that putative ancient peptide segments from the cores of both ribosomal subunits enhance RNA polymerase ribozyme (RPR) function, as do derived homopolymeric peptides comprising lysine or the non-proteinogenic lysine analogues ornithine or, to a lesser extent, diaminobutyric acid, irrespective of chirality or chiral purity. Lysine decapeptides enhance RPR function by promoting holoenzyme assembly through primer–template docking, accelerate RPR evolution, and allow RPR-catalysed RNA synthesis at near physiological (≥1 mM) Mg2+ concentrations, enabling templated RNA synthesis within membranous protocells. Our results outline how compositionally simple, mixed-chirality peptides may have augmented the functional potential of early RNAs and promoted the emergence of the first protocells.

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Figure 1: Ribosomal peptides enhance the activity of an artificial RPR.
Figure 2: RPR activation by homopolymeric peptides.
Figure 3: K10 and [Mg2+] dependence of RPR activity by Z and the evolved 4M.
Figure 4: Robust RNA synthesis during long incubations.
Figure 5: Ribozyme-catalysed RNA synthesis in phospholipid protocells.

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Acknowledgements

The authors thank S. James for assistance with fidelity data processing. This work was supported by postdoctoral fellowships from JSPS (Japanese Society for the Promotion of Science) and HFSP (Human Frontiers Science Program) (S.T.) and by the Medical Research Council (J.A., P.H.; programme no. MC_U105178804).

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S.T. and P.H. conceived and designed the experiments. S.T. performed all experiments together with J.A. for selection design, fidelity measurement and peptide assays. All authors discussed the results and jointly wrote and commented on the manuscript.

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Correspondence to Philipp Holliger.

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Tagami, S., Attwater, J. & Holliger, P. Simple peptides derived from the ribosomal core potentiate RNA polymerase ribozyme function. Nature Chem 9, 325–332 (2017). https://doi.org/10.1038/nchem.2739

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