How was Membrane Permeability Produced in an RNA World?

Abstract

Darwinian evolution in an RNA World required that catalysts be encapsulated in membranes since this would allow superior catalysts to benefit from the products of their own reactions. However, typical membranes are relatively impermeable to polar and complex molecules and, thus, even primitive cells had to have RNA-based mechanisms for the uptake of external nutrients and the excretion of waste products. Nucleic acids form weak non-specific contacts with the surface of the lipid membrane in the presence of divalent cations, and strongly binding species can be obtained in the course of SELEX experiments. The only currently suggested mechanism for the production of permeability is through formation of supramolecular RNA complexes capable of destabilizing and transiently opening lipid membranes by action from one side, but neither natural nor selected examples of RNA channels or transmembrane shuttles are known so far. The necessity to evolve proteins could be strongly driven by the need to build defined hydrophobic structures that when integrated into membranes could provide selective permeability.

The Influence of Environmental Conditions, Lipid Composition, and Phase Behavior on the Origin of Cell Membranes

“…Permeability studies with phospholipid bilayers indicate that amphiphilic composition plays a key role in transport across the membrane (Paula et al 1996;Chakrabarti and Deamer 1992;Deamer 1997;Vlassov 2005;Khvorova et al 1999;Vlassov et al 2001;Janas et al 2004). The chain-length dependence on membrane permeability has already been noted.…”

Re-creating an RNA world

“…Indeed, cofactors for ribozymes appear to be essential for a number of functions, supplementing the limited chemical diversity of RNA [113,114]. One limitation of RNA is its lack of hydrophobic groups, preventing it from efficiently inserting into lipid membranes to form a membrane channel [172]. Although in-vitro-evolved RNA heterotrimers are able to transiently destabilize a lipid membrane and increase permeability for GTP [173], and although membrane permeability for nucleoside phosphates and diphosphates can be increased under narrow physical and chemical conditions [148,149], hydrophobic structures are necessary to generate more efficient membrane channels [172].…”

“…One limitation of RNA is its lack of hydrophobic groups, preventing it from efficiently inserting into lipid membranes to form a membrane channel [172]. Although in-vitro-evolved RNA heterotrimers are able to transiently destabilize a lipid membrane and increase permeability for GTP [173], and although membrane permeability for nucleoside phosphates and diphosphates can be increased under narrow physical and chemical conditions [148,149], hydrophobic structures are necessary to generate more efficient membrane channels [172]. If an array of RNA 2′-hydroxyl groups were decorated with hydrophobic amino acids, this RNA might be able to insert through the membrane and establish a channel (Fig.…”

Novel natural and biomimetic ligands to enhance selectivity of membrane processes for solute‐solute separations: beyond nature's logistic legacy

“…However, bacterial outer membrane porins are specialized in the transport of small organics and some even exhibit polarity‐based separation capabilities. As contemporary cell membranes are virtually impermeable to charged and highly polar solutes, how on earth did protocells then manage to ship around their cargo? Although no natural RNA‐based membrane channels have been identified, artificial RNA constructs have proven that selective transport across the cell membrane is indeed possible . Membrane transport proteins probably gradually outperformed RNA channels due to their much higher chemical diversity resulting in higher tunability for specific transport.…”

“…20 Although no natural RNA-based membrane channels have been identified, artificial RNA constructs have proven that selective transport across the cell membrane is indeed possible. 21,22 Membrane transport proteins probably gradually outperformed RNA channels due to their much higher chemical diversity resulting in higher tunability for specific transport. RNA channels with their highly hydrophilic phosphodiester backbone are also not readily accommodated in the hydrophobic interior of the cell membrane.…”