A small piece of RNA copies itself, hinting at how life first began

In a 1953 experiment, two scientists named Stanley Miller and Harold Urey attempted to recreate the conditions of the early earth long before life existed. They showed that organic molecules such as amino acids, the building blocks of proteins, could form spontaneously in the conditions that prevailed on a primitive earth, 3.5-4 billion years ago.

While the experiment was revolutionary,  it did not settle the question of life’s origins. Critics pointed out that while amino acids could form, there was still no sign of genetic material, i.e. neither DNA nor RNA. Living organisms don’t merely contain proteins: they rely on genetic information encoded in DNA or RNA to build them. Demonstrating that proteins could arise was therefore only part of the story. 

Importantly, life must be able to produce more life. For that, a primitive system would need genetic information and also a way to copy that information. This created a problem. Usually, DNA or RNA stores instructions to make proteins called polymerases. These polymerases then copy the DNA or RNA so that, when a cell divides, each new cell receives a complete set of genetic information. It was and remains a classic chicken-or-egg problem.

Then, in the early 1980s, scientists discovered that RNA itself could perform simple chemical reactions, including being able to cut and paste pieces of itself. This discovery strongly shifted scientists’ thinking towards the possibility that RNA could have been the earliest genetic material on the primitive earth. If a single molecule could both store information and carry out chemical reactions, it could bypass the chicken-and-egg problem of needing proteins to copy genetic material. 

However, while scientists have already developed RNA molecules that could build other RNA molecules, they still lack an RNA that could copy the information contained within itself. The difficulty was structural: the RNA enzymes capable of copying other RNAs were large and complex — between 150-300 nucleotides — and in trying to fold into their functional shapes they could not easily serve as templates for their own replication. In other words, RNA could help other proteins replicate but couldn’t self-replicate.

Now, however, in a paper in Science, scientists from the MRC Laboratory of Molecular Biology in the U.K. have reported that they have generated a self-replicating RNA molecule. Specifically, the researchers produced a small RNA molecule, just 45 nucleotides long, that could copy its own genetic information.

To do this, they first sifted through enormous pools of RNAs, building on earlier work with much larger RNA enzymes, and repeatedly selected those rare sequences that showed even faint signs of replication. This led to the development of QT45, which is, according to the researchers, the world’s first RNA molecule that can make copies of itself.

However, while the QT45 RNA can do this, its process of self-replication was extraordinarily slow and required special conditions. Producing a single full-length copy took weeks. In contrast, modern cellular polymerases can copy 45 nucleotides in less than a second. Though the difference is dramatic, primitive earth had millions of years, so even QT45’s stringent and slow copying conditions could realistically have occurred and been sustained.

Also, modern enzymes add nucleotides one at a time, reading the template, and making a new chain of complementary nucleotides. QT45 used short three-nucleotide building blocks, even if it also followed the same logic: it first assembled a complementary negative strand, then used that as the template to reproduce the original copy.

However, the most striking, and in many ways the most beautiful, feature of the QT45 RNA was that it was imperfect. Its copying accuracy was only about 92-94%. This means it makes mistakes when replicating the genetic information, a property at the core of a true copying system. Every mistake creates variation, and variations are the raw material upon which natural selection can act.

While the development of the QT45 RNA is indeed a breakthrough, it is important to remember that while it strengthens RNA’s case as the first genetic material, it doesn’t prove it. QT45 merely shows that self-replicating RNAs can exist and that that could be the way in which life on the earth first began.

The exact manner in which life originated may remain lost to history forever, but discoveries like QT45 show that inert matter can sometimes begin to behave like life. At the heart of it, it’s just chemistry, slowly learning to remember itself.

Arun Panchapakesan is an assistant professor at the Y.R. Gaitonde Centre for AIDS Research and Education, Chennai.

Published – February 25, 2026 07:00 am IST