Samanta Pino

Generation of Long RNA Chains in Water

The synthesis of RNA chains from 3′,5′-cAMP and 3′,5′-cGMP was observed. The RNA chains formed in water, at moderate temperatures (40–90 °C), in the absence of enzymes or inorganic catalysts. As determined by RNase analyses, the bonds formed were canonical 3′,5′-phosphodiester bonds. The polymerizations are based on two reactions not previously described: 1) oligomerization of 3′, 5′-cGMP to ∼25-nucleotide-long RNA molecules, and of 3′,5′-cAMP to 4- to 8-nucleotide-long molecules. Oligonucleotide A molecules were further extended by reciprocal terminal ligation to yield RNA molecules up to >120 nucleotides long and 2) chain extension by terminal ligation of newly polymerized products of 3′,5′-cGMP on preformed oligonucleotides. The enzyme- and template-independent synthesis of long oligomers in water from prebiotically affordable precursors approaches the concept of spontaneous generation of (pre)genetic information.

From formamide to RNA: the roles of formamide and water in the evolution of chemical information

In pursuing the origin of informational polymers, we followed the assumption that their spontaneous formation could only have occurred: (i) if all the components were present at the same site and in the same reaction, and (ii) if the thermodynamics of the processes involved favored a polymerized over a monomeric state of the precursors. A plausible scenario satisfying both assumptions is provided.

Nonenzymatic RNA Ligation in Water

We describe the nonenzymatic ligation of RNA oligomers in water. Dimers and tetramers are formed in a time-, pH-, and temperature-dependent reaction. Ligation efficiency depends on oligonucleotide length and sequence and is strongly enhanced by adenine-based nucleotide cofactors. Ligation of short RNA fragments could have liberated the prebiotic polymerization systems from the thermodynamically demanding task of reaching a (pre)genetically meaningful size by stepwise addition of one precursor monomer at the time.

Generation of RNA Molecules by a Base-Catalysed Click-Like Reaction

The problem of the abiotic origin of RNA from prebiotically plausible compounds remains unsolved. As a potential partial solution, we report the spontaneous polymerization of 3′,5′‐cyclic GMP in water, in formamide, in dimethylformamide, and (in water) in the presence of a Brønsted base such as 1,8‐diazabicycloundec‐7‐ene. The reaction is untemplated, does not require enzymatic activities, is thermodynamically favoured and selectively yields 3′,5′‐bonded ribopolymers containing as many as 25 nucleotides. We propose a reaction pathway on the basis of 1) the measured stacking of the 3′,5′‐cyclic monomers, 2) the activation by Brønsted bases, 3) the determination (by MALDI‐TOF mass spectrometry, by 31P NMR, and by specific ribonucleases) of the molecular species produced. The reaction pathway has several of the attributes of a click‐like reaction.

From Formamide to RNA, the Path Is Tenuous but Continuous

Reactions of formamide (NH2COH) in the presence of catalysts of both terrestrial and meteoritic origin yield, in plausible and variegated conditions, a large panel of precursors of (pre)genetic and (pre)metabolic interest. Formamide chemistry potentially satisfies all of the steps from the very initial precursors to RNA. Water chemistry enters the scene in RNA non-enzymatic synthesis and recombination.

Sequence complementarity-driven nonenzymatic ligation of RNA

We report two reactions of RNA G:C sequences occurring nonenzymatically in water in the absence of any added cofactor or metal ion: (a) sequence complementarity-driven terminal ligation and (b) complementary sequence adaptor-driven multiple tandemization. The two abiotic reactions increase the chemical complexity of the resulting pool of RNA molecules and change the Shannon information of the initial population of sequences.

Emergence of the First Catalytic Oligonucleotides in a Formamide‐Based Origin Scenario

50 years after the historical Miller-Urey experiment, the formamide-based scenario is perhaps the most powerful concurrent hypothesis for the origin of life on our planet besides the traditional HCN-based concept. The information accumulated during the last 15 years in this topic is astonishingly growing and nowadays the formamide-based model represents one of the most complete and coherent pathways leading from simple prebiotic precursors up to the first catalytically active RNA molecules. In this work, we overview the major events of this long pathway that have emerged from recent experimental and theoretical studies, mainly concentrating on the mechanistic, methodological, and structural aspects of this research.

On the Observable Transition to Living Matter

In recent developments in chemistry and genetic engineering, the humble researcher dealing with the origin of life finds her(him)self in a grey area of tackling something that even does not yet have a clear definition agreed upon. A series of chemical steps is described to be considered as the life–nonlife transition, if one adheres to the minimalistic definition: life is self-reproduction with variations. The fully artificial RNA system chosen for the exploration corresponds sequence-wise to the reconstructed initial triplet repeats, presumably corresponding to the earliest protein-coding molecules. The demonstrated occurrence of the mismatches (variations) in otherwise complementary syntheses (“self-reproduction”), in this RNA system, opens an experimental and conceptual perspective to explore the origin of life (and its definition), on the apparent edge of the origin.

Materials for the onset. A story of necessity and chance.

We review the reactions that take place in the HCN/NH2COH/catalysts system. In a vision of origin-of-life as emergence of new properties in complexity, the effectiveness of HCN/NH2COH chemistry is so robust and variegate to look unreasonable. In a logic close to Occamian simplicity, this chemistry embodies necessity. The evolution of the necessary fruits of this chemistry towards organismic level entails Darwinism. The role of chance enters into the process as an answer to evolving environments.

May Cyclic Nucleotides Be a Source for Abiotic RNA Synthesis

Nucleic bases are obtained by heating formamide in the presence of various catalysts. Formamide chemistry also allows the formation of acyclonucleosides and the phosphorylation of nucleosides in every possible position, also affording 2′,3′ and 3′,5′ cyclic forms. We have reported that 3′,5′ cyclic GMP and 3′,5′ cyclic AMP polymerize in abiotic conditions yielding short oligonucleotides. The characterization of this reaction is being pursued, several of its parameters have been determined and experimental caveats are reported. The yield of non-enzymatic polymerization of cyclic purine nucleotides is very low. Polymerization is strongly enhanced by the presence of base-complementary RNA sequences.