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Inosine, RNA and the Origins of Life:


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https://phys.org/news/2018-12-inosine-potential-route-rna-life.html

Inosine could be a potential route to the first RNA and the origin of life on Earth

December 3, 2018, Harvard University:

Life has a new ingredient

Somewhere in the hostile environment of early Earth, life was born. Credit: Harvard University

Our prehistoric Earth, bombarded with asteroids and lightening, rife with bubbling geothermal pools, may not seem hospitable today. But somewhere in the chemical chaos of our early planet, life did form. How? For decades, scientists have attempted to create miniature replicas of infant Earth in the lab. There, they hunt for the primordial ingredients that created the essential building blocks for life.

It's attractive to chase our origin story. But this pursuit can bring more than just thrill. Knowledge of how Earth built its first cells could inform our search for extraterrestrial life. If we identify the ingredients and environment required to spark spontaneous life, we could search for similar conditions on planets across our universe.

Today, much of the origin-of-life research focuses on one specific building block: RNA. While some scientists believe that life formed from simpler molecules and only later evolved RNA, others look for evidence to prove (or disprove) that RNA formed first. A complex but versatile molecule, RNA stores and transmits genetic information and helps synthesize proteins, making it a capable candidate for the backbone of the first cells.

Read more at: https://phys.org/news/2018-12-inosine-potential-route-rna-life.html#jCp

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the paper:

http://www.pnas.org/content/early/2018/11/26/1814367115

Abstract

The emergence of primordial RNA-based life would have required the abiotic synthesis of nucleotides, and their participation in nonenzymatic RNA replication. Although considerable progress has been made toward potentially prebiotic syntheses of the pyrimidine nucleotides (C and U) and their 2-thio variants, efficient routes to the canonical purine nucleotides (A and G) remain elusive. Reported syntheses are low yielding and generate a large number of undesired side products. Recently, a potentially prebiotic pathway to 8-oxo-adenosine and 8-oxo-inosine has been demonstrated, raising the question of the suitability of the 8-oxo-purines as substrates for prebiotic RNA replication. Here we show that the 8-oxo-purine nucleotides are poor substrates for nonenzymatic RNA primer extension, both as activated monomers and when present in the template strand; their presence at the end of a primer also strongly reduces the rate and fidelity of primer extension. To provide a proper comparison with 8-oxo-inosine, we also examined primer extension reactions with inosine, and found that inosine exhibits surprisingly rapid and accurate nonenzymatic RNA copying. We propose that inosine, which can be derived from adenosine by deamination, could have acted as a surrogate for G in the earliest stages of the emergence of life.

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