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Biologists create self-replicating RNA molecule
Apr 07, 2011

It doesn't have a very sexy name, but tC19Z, synthesised in a lab in Cambridge, UK, could be a version of one of the first enzymes that ever existed on our planet - and a clue to how life itself got started.

A prominent theory of how life started involves the appearance of a self-replicator - some kind of simple molecule that was capable of making copies of itself without relying on other molecules. The trouble is, if this self-replicating molecule ever did exist, it doesn't any more. The vast majority of organisms around today use DNA to store their genetic information, and DNA does not copy itself - other enzymes do that bit for it.

Enter tC19Z. Built by Philipp Holliger and colleagues, it is an RNA enzyme that functions like a self-replicator.

RNA is structurally similar to DNA and can also be used to store genetic information. Some RNA molecules can act as enzymes, driving important chemical reactions in cells, but an RNA enzyme that can reliably copy other RNA segments, let alone self-replicate, has proved elusive.

Until now, the only known RNA-copying RNA was a molecule called R18, which can only copy RNA segments up to 14 "letters" long, and only works on certain sequences. It's like a word processor that can copy-and-paste "turnip" but not "swede".

Holliger, who is based at the MRC Laboratory of Molecular Biology in Cambridge, UK, has now set out to improve R18. He made a vast library of thousands of different versions of the molecule and screened them to see which ones made more copies. After several rounds of copying variants and looking for new improvements, he found several useful tweaks, which he incorporated into his final patchwork enzyme, tC19Z.

tC19Z can reliably copy RNA sequences up to 95 letters long, a near-sevenfold increase on R18. Its performance varies depending on the sequence it's copying, but it is much less picky than R18. Holliger compares R18 to a sports car that works only on a smooth, flat road. "We have fitted a four-wheel drive, so it can go off-road a bit," he says.

Crucially, tC19Z can copy pieces of RNA that are almost half as long (48 per cent) as itself. If an RNA enzyme is to copy itself, it has to be able to copy sequences as long as itself, and tC19Z is closing in on that goal.

In a neat twist, Holliger's team also showed that tC19Z can make copies of another RNA enzyme, which then worked correctly. That suggests that, once the first self-replicating RNA had appeared, it would have been able to surround itself with additional molecular equipment, kick-starting the evolution of more complex life.



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