4.8 Article

Hydrophobic-cationic peptides modulate RNA polymerase ribozyme activity by accretion

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NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41467-022-30590-3

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资金

  1. JSPS (Japanese Society for the Promotion of Science)
  2. HFSP (Human Frontiers Science Program)
  3. Medical Research Council (MRC) program [MC_U105178804]
  4. JSPS [20K14599, 18H01328]
  5. Astrobiology Center of National Institutes of Natural Sciences [AB301005]
  6. Grants-in-Aid for Scientific Research [20K14599, 18H01328] Funding Source: KAKEN
  7. MRC [MC_U105178804] Funding Source: UKRI

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Macromolecular aggregates are believed to have played a crucial role in the origin of life. This study reveals that hydrophobic-cationic peptides can form insoluble aggregates that reversibly bind to RNA and enhance RNA polymerization, suggesting their potential contribution to the emergence and evolution of longer, functional RNAs in the early Earth.
Macromolecular aggregates may have played an important role in the origin of life. Here, the authors report hydrophobic-cationic peptides that form insoluble aggregates, which reversibly accrete RNA on their surfaces, and enhance RNA polymerization by a ribozyme. Accretion and the resulting increase in local concentration is a widespread mechanism in biology to enhance biomolecular functions (for example, in liquid-liquid demixing phases). Such macromolecular aggregation phases (e.g., coacervates, amyloids) may also have played a role in the origin of life. Here, we report that a hydrophobic-cationic RNA binding peptide selected by phage display (P43: AKKVWIIMGGS) forms insoluble amyloid-containing aggregates, which reversibly accrete RNA on their surfaces in an RNA-length and Mg2+-concentration dependent manner. The aggregates formed by P43 or its sequence-simplified version (K2V6: KKVVVVVV) inhibited RNA polymerase ribozyme (RPR) activity at 25 mM MgCl2, while enhancing it significantly at 400 mM MgCl2. Our work shows that such hydrophobic-cationic peptide aggregates can reversibly concentrate RNA and enhance the RPR activity, and suggests that they could have aided the emergence and evolution of longer and functional RNAs in the fluctuating environments of the prebiotic earth.

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