There is ample evidence that RNA played a central role in information storage and

catalysis during early biology [1]. However, all known ribozymes at dilution, far below their KM (Michaelis-Menten constant), are prone to adopt inactive conformations and require unrealistically high RNA and metal-salt concentration to overcome inactive conformations and achieve high levels of activity [2, 3, 4]. Herein, we show that ppm-amounts of various noncharged water soluble polymers, such as, PEG (polyethylene glycol), PVA (polyvinyl alcohol) and others act as chemical chaperones that enable strong ribozyme activity even at nanomolar RNA and suboptimal salt concentrations. Specifically, we find that for diluted multi-component RNA ligases (R3C) [5] and RNA cleaving ribozymes (HH) [4, 6] ppm amounts of PEG 10K boost ribozyme-substrate interactions by almost two orders of magnitude and extend the lifetime of the reactions resulting in up to 12-fold and 6-fold higher product yields, respectively. Furthermore, these findings imply that trace amounts of suitable polymers in a primitive environment may have been sufficient to boost early bio-catalysis by orders of magnitude.

 

1. Gesteland RF, Cech T, Atkins JF, Laboratory CSH. The RNA World: The Nature of Modern

RNA Suggests a Prebiotic RNA World. Cold Spring Harbor Laboratory Press, 2006.

2. Paudel BP, Rueda D. Molecular Crowding Accelerates Ribozyme Docking and Catalysis.

Journal of the American Chemical Society 2014, 136(48): 16700-16703.

3. Kilburn D, Roh JH, Guo L, Briber RM, Woodson SA. Molecular Crowding Stabilizes Folded

RNA Structure by the Excluded Volume Effect. Journal of the American Chemical Society

2010, 132(25): 8690-8696.

4. Nakano S-i, Karimata HT, Kitagawa Y, Sugimoto N. Facilitation of RNA Enzyme Activity in

the Molecular Crowding Media of Cosolutes. Journal of the American Chemical Society 2009,

131(46): 16881-16888.

5. Lincoln TA, Joyce GF. Self-Sustained Replication of an RNA Enzyme. Science 2009,

323(5918): 1229.

6. Drobot B, Iglesias-Artola JM, Le Vay K, Mayr V, Kar M, Kreysing M, et al. Compartmentalised

RNA catalysis in membrane-free coacervate protocells. Nature Communications 2018, 9(1):

3643.