Biochemistry & Organic Chemistry

Prebiotic Synthesis of RNA Nucleotides

By Keith Cowing
Press Release
January 17, 2018
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Prebiotic Synthesis of RNA Nucleotides
The basic constituents of the earliest RNA molecules may have formed in a geothermal environment, such that seen here in Yellowstone National Park in Wyoming.
National Park Service

RNA was probably the first informational molecule. Now chemists from Ludwig-Maximilians-Universitaet (LMU) in Munich have demonstrated that alternation of wet and dry conditions could have sufficed to drive the prebiotic synthesis of the RNA nucleosides found in all domains of life.

“And the Earth was without form and void” – before the emergence of life. Meanwhile, we know rather more about the early Earth, but how might the chemical structures that provide the basic subunits of today’s hereditary molecules – RNA and DNA – have formed from simpler starting materials some 4 billion years ago? Under what conditions could these building blocks have then been linked into long chains that could not only encode information but also propagate it by self-reproduction? Many possible scenarios have been proposed for the phase of chemical evolution that preceded the emergence of the first biological cells. Now, researchers led by LMU chemist Professor Thomas Carell have extended these models by demonstrating a plausible route for the prebiotic synthesis of the ‘nucleosides’ that constitute the informational components of RNA.

Specifically, Carell and his colleagues have shown that nucleosides can be formed in a continuous process by exposing simple chemicals to the kinds of fluctuating physical conditions that would have prevailed in geothermally active areas characterized by volcanic activity on the early Earth. They begin with a mixture of formic acid, acetic acid, sodium nitrite and a few nitrogen-containing compounds, all of which have previously been shown to form from even simpler precursors under prebiotic conditions. The reaction mixture also contained nickel and iron, which are found in large amounts in the Earth’s crust. The driving force for the chemical reactions is supplied by fluctuations in temperature and pH, together with wet/dry cycles, such as those that occur in the vicinity of periodically active hot springs or in strongly seasonal climates with alternating periods of precipitation and evaporation.

The core of the process is a series of reactions that gives rise to compounds called formamidopyrimidines, which can in turn be converted into the canonical purines (adenosine and guanosine) found in RNA. In a paper published last year, Carell and his team first described this FaPy pathway as a possible chemical scenario for the prebiotic synthesis of nucleosides. “This time around, we not only began with simpler precursor compounds, but chose conditions that would be expected to prevail in a plausible geological setting, such as hydrothermal springs on land,” explains Sidney Becker, a PhD student in Carell’s group and first author of the study. The paper has now appeared in one of the leading online, open-access journals, Nature Communications.

Notably, not only the canonical purine nucleosides found in RNA were synthesized in the new experiments, but also a whole series of closely related molecules. Even more strikingly, all of the modifications observed are known to occur in RNAs in all three domains of life – Eukaryota (animals and plants), Bacteria and Archaea – and are therefore essential components of functional genetic systems. Hence, they were most probably already present in the last common ancestor of all life forms. This in turn argues, says Becker, that these compounds must have been available on early Earth when biological evolution began. Indeed, the authors of the new study suggest that the non-canonical nucleosides could have played a crucial role in the phase of chemical evolution that preceded the emergence of the ‘RNA world’ (the term refers to a hypothetical period during which RNA molecules are thought to have served as chemical catalysts, in addition to storing genetic information, in primordial cells). Seen in this light, the RNA modifications found in today’s organisms represent molecular fossils that have continued to participate in vital biological functions for billions of years.

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