Primordial RNA May Have Contained Inosine
Primordial RNA May Have Contained Inosine

Primordial RNA May Have Contained Inosine

The discovery that the adenosine derivative aids self-replication adds weight to the theory that life on Earth originated from a mixture of RNA molecules.

Mar 1, 2019
Catherine Offord

ABOVE: A primordial version of RNA might have incorporated inosine, a derivative of adenosine, in place of guanosine.
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The paper
S.C. Kim et al., “Inosine, but none of the 8-oxo-purines, is a plausible component of a primordial version of RNA,” PNAS, 115:13318–23, 2018.

Proponents of the RNA world theory argue that life on Earth originated from a mixture of self-replicating, information-storing molecules. But while researchers have discovered ways that RNA’s pyrimidine nucleosides, uridine and cytidine, could have formed in primordial conditions, they’ve had less success with the purine nucleosides adenosine and guanosine, casting the theory into doubt.

Biologist Jack Szostak’s lab at Harvard Medical School recently set out to test a new hypothesis: that compounds called 8-oxo-purines could have acted as substitutes for modern purines in primordial RNA. His team used an adenosine derivative, inosine, as a control.

Under early-Earth conditions, 8-oxo-purines turned out to perform poorly—RNA molecules containing them copied slowly and with low accuracy. But inosine, unexpectedly, served as an excellent guanosine substitute. “We were really surprised to see that actually inosine works almost as well as guanosine, and in some cases, slightly better,” says Szostak. While it’s impossible to confirm that inosine really was a component of primordial RNA, “we’re pretty convinced that it could have happened this way.”

By removing the need for a plausible chemical pathway to generate guanosine under early-Earth conditions, the paper “goes a long way to suggesting a solution to a long-standing problem,” says John Sutherland, a chemist at the MRC Laboratory of Molecular Biology at the University of Cambridge who was not involved in the work but, like Szostak, is part of the Simons Collaboration on the Origins of Life.

Researchers now need only to find out how adenosine could have formed in order to complete the story of how primordial RNA might have come together. “The value of this work is not just in what [Szostak’s group] does next,” says Sutherland, “but what it suggests other people should do next as well.”