Wednesday , May 12 2021

Inosine may be a potential route to the first RNA and the origin of life on Earth – ScienceDaily



Our prehistoric earth, bombarded with asteroids and lighting, widespread by shooting geothermal pools, may not look an atmosphere today. But somewhere in the chemical chaos of our early planet, life is formed. How? For decades, scientists have tried to create miniature replicas of infants Earth in the laboratory. There, they hunt for the primordial ingredients that created the basic building blocks for life.

It is attractive to chase away our story of origin. But this quest can bring more than just excitement. Knowing how Earth has built up its first cells can inform our search for extraterrestrial life. If we identify the constituents and environment necessary to cause spontaneous life, we could seek similar conditions on planets throughout our universe.

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

To confirm this "RNA World Hypothesis," researchers face two challenges. First, they need to identify which ingredients have reacted to the creation of four nucleotides of RNA – adenine, guanine, cytosine, and uracil (A, G, C and U). Second, they need to determine how RNA stores and copies genetic information in order to replicate themselves.

So far, scientists have made significant progress in discovering the precursors of C and U. But, A and G remain elusive. Now, in a paper published in PNAS, Jack V. Shostak, a professor of chemistry and chemical biology at Harvard University, along with Seohyun's first undergraduate student and student at the undergraduate studies, suggests that RNA can start with a different set of nucleotide bases. Instead of guanine, RNA could rely on a surrogate – inosine.

"Our study suggests that the earliest forms of life (with A, U, C, and I) may emerge from a different set of nucleobases from those found in modern life (A, U, C, and G)," said Kim. How did he and his team come to this conclusion? Laboratory attempts to deposit A ​​and G, purine-based nucleotides, produced too many side products. However, recently, researchers have discovered a way to make versions of adenosine and inosine – 8-oxoadenosine and 8-oxo-inosine – from materials available in the original Earth. So, Kim and his colleagues began to explore whether the RNA built with these analogues can be replicated efficiently.

But replacements failed to fulfill them. As a cake baked with honey instead of sugar, the final product may seem to taste similar, but it does not work as well. The copper cake burns and dips into the liquid. 8-oxo-purine RNA is still functioning, but loses the speed and accuracy needed to copy. If it is played too slowly, it decays before the process is complete. If it makes too many mistakes, it can not serve as a reliable tool for propagation and evolution.

Despite their improper performance, the 8-oxo-purines brought unexpected surprise. As part of the test, the team compared the capabilities of 8-oxo-inosine against control, inosine. Unlike its 8-oxo counterpart, inosine allows RNA to replicate at high speed and several faults. "It turns out that it exhibits reasonable rates and fidelity in RNA copying reactions," the team concluded. "We suggest that inosine could serve as a surrogate for guanosine in the early onset of life."

The discovery of Shostak and Kim could help substantiate the hypothesis of the world of RNA. Over time, their work can confirm the basic role of RNA in our story of origin. Or, scientists can discover that Early Earth has offered more pathways for life to grow. Finally, armed with this knowledge, scientists could identify other planets that have the essential ingredients and determine whether we share this universe or, in fact, we are alone.


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