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Tiny, 45 base long RNA can make copies of itself

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There are plenty of unanswered questions about the origin of life on Earth. But the research community has largely reached consensus that one of the key steps was the emergence of an RNA molecule that could replicate itself. RNA, like its more famous relative DNA, can carry genetic information. But it can also fold up into three-dimensional structures that act as catalysts. These two features have led to the suggestion that early life was protein-free, with RNA handling both heredity and catalyzing a simple metabolism.

For this to work, one of the reactions that the early RNAs would need to catalyze is the copying of RNA molecules, without which any sort of heritability would be impossible. While we’ve found a number of catalytic RNAs that can copy other molecules, none have been able to perform a key reaction: making a copy of themselves. Now, however, a team has found an incredibly short piece of RNA—just 45 bases long—that can make a copy of itself.

Finding an RNA polymerase

We have identified a large number of catalytic RNAs (generically called ribozymes, for RNA-based enzymes), and some of them can catalyze reactions involving other RNAs. A handful of these are ligases, which link together two RNA molecules. In some cases, they need these molecules to be held together by a third RNA molecule that base pairs with both of them. We’ve only identified a few that can act as polymerases, which add RNA bases to a growing molecule, one at a time, with each new addition base pairing with a template molecule.

Credit: John Timmer Some ligases can link two nucleic acid strands (left), while others can link the strands only if they’re held together by base pairing with a template (center). A polymerase can be thought of as a template-dependent ligase that adds one base at a time. The newly discovered ribozyme sits somewhere between a template-directed ligase and a polymerase. Some ligases can link two nucleic acid strands (left), while others can link the strands only if they’re held together by base pairing with a template (center). A polymerase can be thought of as a template-dependent ligase that adds one base at a time. The newly discovered ribozyme sits somewhere between a template-directed ligase and a polymerase. Credit: John Timmer

Obviously, there is some functional overlap between them, as you can think of a polymerase as ligating on one base at a time. And in fact, at the ribozyme level, there’s some real-world overlap, as some ribozymes that were first identified as ligases were converted into polymerases by selecting for this new function.