RNA-Like Molecules Found to Self-Assemble into Gene-Like Material – Discovery May Be Key to the Origin of Life

 

proto-RNA self-assembling into genetic material
Proto-RNA? Chemicals known as TAPAS and CA (left) assemble together forming rosettes (middle) that then stack into genelike chains (right). Credit: B.J. Cafferty et al., JACS (2013)

In the great quest to uncover the secrets to the origin of life on Earth — a discipline referred to as biogenesis theory — there remains a profound (unanswered) question: how do “living” molecules arise from non-living ones? For, to answer such a question means making a distinction between different states of molecular organization. The question is almost metaphysical in nature — for it requires one to ponder the very definition of ‘Life’; it is nearly impossible to pinpoint a particular stage (or molecular structure) in the genesis of living matter and say this is now “alive”, when previously, it was “non-living” (e.g., Is it only the cell that is alive? What about mitochondria which also have DNA? What about the ribosomes that translate RNA messages into proteins?, etc.)

But there are a few requirements for living matter that scientists do recognize; such living molecules must possess two fundamental features: they must be capable of “self-organization” (also called “self-assembly”) under the right environmental conditions, and, they must be capable of self-replication. This last feature is tricky, since it implies that there is some form of “molecular memory”, or information coding, at work, such that these special molecules can remember how to copy themselves.

The RNA World hypothesis

The most promising candidate molecules here are RNA (ribonucleic acid) molecules which are both simpler than DNA molecules and more powerful catalysts for molecular interactions. Indeed, RNA-based enzymes (i.e., the RNA polymerases) are necessary for DNA replication. Many biologists believe that some form of RNA — or precursors to RNA — had to evolve first, before the more complex DNA molecule could appear. This view is known as the ‘RNA World’ hypothesis.

But, there’s one big problem with the RNA World hypothesis; the building blocks of RNA — the nucleoside bases cytosine (C), guanine (G), adenine (A) and urasil (U) — do not normally assemble themselves into longer chains to form the genetic structures we associate with living molecules.

This has led many scientists to posit precursors to these RNA bases — proto-RNAs — that must have evolved first. According to Nicholas Hud, a chemist at the Georgia Institute of Technology (Georgia Tech) in Atlanta, “RNA is so perfect today that it has to be the product of evolution”

The Experiments with “Proto-RNA” Molecules

To test this theory, Georgia Tech researchers, collaborating with colleagues from the Institute for Research in Biomedicine in Barcelona, Spain, began a series of experiments with two key proto-RNA candidate molecules: cyanuric acid (CA) and triaminopyrimidine (TAP). The latter molecule belongs to a family of chemicals called pyrimidines of which the RNA bases C and U are members. CA is also structurally related to the pyrimidines. Earlier research had shown that these molecules spontaneously formed ring-like structures called rosettes — when immerse in an organic solvent medium. Successive rosettes would stick together to form stacks — compound structures that bear some resemblance to how genetic material is built up from simpler, repetitive structures.

However, the research team found that, in water, TAP and CA simply clump together into ribbons and sheets and then fall out of solution — what’s known as the “hydrophobic effect” — which is not a good result for molecules that supposedly give rise to RNAs (which must also store genetic information).
Testing these molecules in water is significant, given the notion of a “primordial soup” — the primordial, watery ecosystem (a pond, lake, tide pool, or even deep sea vent) that is posited to have been the matrix of living molecules. Yet, when placed in water, these would-be RNA precursors failed to form into more complex structures.
But further testing led researcher to a solution for this “solution problem.” The team devised a chemical structure — a short “tail” — that, when attached to TAP, stimulated it to assemble with with CA to form the rosette structures they were looking for. The new molecule was dubbed TAPAS. further, the rosettes then began stacking one atop the other — forming longer, more complex chains of gene-like material. Some of these chains possessed over 18,000 individual units of TAPAS and CA. The researchers described this as “highly cooperative self-assembly.”
Quoting from the published report (abstract):
“Two weakly interacting low-molecular-weight monomers (cyanuric acid and a modified triaminopyrimidine) are shown to form extremely long supramolecular polymer assemblies that retain water solubility. The complete absence of intermediate assemblies means that the observed equilibrium is between free monomers and supramolecular assemblies…[content edited]
The results of our study have implications for the design of new self-assembling structures and hydrogel-forming molecules and may provide insights into the origin of the first RNA-like polymers.”
What’s Next for Biogenesis Experiments?
So, researchers have, at last, achieved molecular self-assembly (of “proto-RNA”) in water.
However, what still remains to be seen is whether or not this two-molecule, self-assembly system can somehow encode information — the molecular memory requirement of living matter — which would potentially drive these molecules towards a structures resembling actual RNA.
And, even if this feat is achieved, it will not prove that this is how life arose from the primordial soup…but it will demonstrate one path that key molecules may have taken on the long journey of becoming living matter.
Scientific team members included: Brian J. Cafferty, Isaac Gállego, Michael C. Chen, Katherine I. Farley, Ramon Eritja, and Nicholas V. Hud.

The paper entitled ‘Efficient Self-Assembly in Water of Long Noncovalent Polymers by Nucleobase Analogues’ was published February 8th in the Journal of the American Chemical Society.

For further reading on the subject of biogenesis, check out my earlier article In Search of Ancient Alien Microbes & the Origin of Life.

Main Reference for this post: ‘Self-Assembling Molecules Offer New Clues on Life’s Possible Origin’ by Robert F. Service

Top Image: (RNA-like molecules self-assemble into gene-like structures in water); Credit: B.J. Cafferty et al., JACS (2013)

 

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