A pinboard by
Angelica Mariani

I am a postdoctoral researcher working on the chemical origin of life at the MRC-LMB (Cambridge, UK)


Non-enzymatic recycling for the degradation and repair of unnatural RNA on the early Earth

How did life start on Earth?

Researchers from all over the world are currently involved in finding an answer to the big question of the origin of life. From a chemistry perspective, the best clues can be found in the intrinsic reactivity of the molecules that were present on the early Earth and current investigations are focused on understanding how these molecules combined to form the building blocks of modern biology.

Why RNA?

RNA is a central molecule in life, able to both store genetic information and catalyze biological reactions. Understanding how RNA arose and evolved in a prebiotic context is one of the major challenges of the origin of life research.

What is my research about?

In biology, RNA comprises building blocks joined by 3′,5′-linkages, but unnatural 2′,5′-linkages are also chemically possible and ribonucleic acid containing both types of linkages is the expected product of prebiotic chemistry on the early Earth. How backbone heterogeneous ribonucleic acid became modern RNA is thus central to the origin of life question. We designed and experimentally demonstrate a model in which unnatural linkages can be converted to the natural linkages of RNA by a non-enzymatic process of degradation and repair, defining a plausible recycling scenario for the prebiotic evolution of ribonucleic acid.


Evolution of functional nucleic acids in the presence of nonheritable backbone heterogeneity.

Abstract: Multiple lines of evidence support the hypothesis that the early evolution of life was dominated by RNA, which can both transfer information from generation to generation through replication directed by base-pairing, and carry out biochemical activities by folding into functional structures. To understand how life emerged from prebiotic chemistry we must therefore explain the steps that led to the emergence of the RNA world, and in particular, the synthesis of RNA. The generation of pools of highly pure ribonucleotides on the early Earth seems unlikely, but the presence of alternative nucleotides would support the assembly of nucleic acid polymers containing nonheritable backbone heterogeneity. We suggest that homogeneous monomers might not have been necessary if populations of heterogeneous nucleic acid molecules could evolve reproducible function. For such evolution to be possible, function would have to be maintained despite the repeated scrambling of backbone chemistry from generation to generation. We have tested this possibility in a simplified model system, by using a T7 RNA polymerase variant capable of transcribing nucleic acids that contain an approximately 11 mixture of deoxy- and ribonucleotides. We readily isolated nucleotide-binding aptamers by utilizing an in vitro selection process that shuffles the order of deoxy- and ribonucleotides in each round. We describe two such RNA/DNA mosaic nucleic acid aptamers that specifically bind ATP and GTP, respectively. We conclude that nonheritable variations in nucleic acid backbone structure may not have posed an insurmountable barrier to the emergence of functionality in early nucleic acids.

Pub.: 10 Aug '11, Pinned: 30 Jun '17

Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions.

Abstract: At some stage in the origin of life, an informational polymer must have arisen by purely chemical means. According to one version of the 'RNA world' hypothesis this polymer was RNA, but attempts to provide experimental support for this have failed. In particular, although there has been some success demonstrating that 'activated' ribonucleotides can polymerize to form RNA, it is far from obvious how such ribonucleotides could have formed from their constituent parts (ribose and nucleobases). Ribose is difficult to form selectively, and the addition of nucleobases to ribose is inefficient in the case of purines and does not occur at all in the case of the canonical pyrimidines. Here we show that activated pyrimidine ribonucleotides can be formed in a short sequence that bypasses free ribose and the nucleobases, and instead proceeds through arabinose amino-oxazoline and anhydronucleoside intermediates. The starting materials for the synthesis-cyanamide, cyanoacetylene, glycolaldehyde, glyceraldehyde and inorganic phosphate-are plausible prebiotic feedstock molecules, and the conditions of the synthesis are consistent with potential early-Earth geochemical models. Although inorganic phosphate is only incorporated into the nucleotides at a late stage of the sequence, its presence from the start is essential as it controls three reactions in the earlier stages by acting as a general acid/base catalyst, a nucleophilic catalyst, a pH buffer and a chemical buffer. For prebiotic reaction sequences, our results highlight the importance of working with mixed chemical systems in which reactants for a particular reaction step can also control other steps.

Pub.: 16 May '09, Pinned: 22 Jun '17