Nature
PUBLISHED
As someone who’s sat through many molecular biology lectures, I can reliably inform you that students are repeatedly told what’s said to be a fundamental rule about DNA: to make more of it, it has to be copied from a template. At least, scientists thought that was the case. Not so, say the researchers who’ve just discovered a bacterial defense system that appears to do things differently.
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There are two templates that might be used to make new DNA. The first is DNA itself; this involves a sequence of enzymes first “unzipping” the DNA (a double-stranded helix), then pairing up new nucleotides – the classic A, T, C, and G – with those on the separated strands (As with Ts, Cs with Gs), and Bob’s your uncle, you’ve now got two identical DNA molecules.
Then there’s RNA. In this case, a nifty little group of enzymes called reverse transcriptases are the ones adding on the nucleotides to the single-stranded RNA, transforming it into a double-stranded bit of DNA. It’s this method that HIV uses to convert its RNA genome into DNA and hijack the cellular machinery of its hosts.
A different approach
Reverse transcriptases don’t take sides, however; bacteria can also make use of them to fight viruses – specifically the group of viruses known as phages, which exclusively infect bacteria. That’s the role they play in DRT3, the defense system that’s just been discovered in bacteria by Stanford University scientists.
DRT3 is a complex made up of three different kinds of molecules: two are reverse transcriptases and the other noncoding RNA. Using a method called cryo-electron microscopy, the team were able to see that the complex has six copies of each, arranged symmetrically.
One of the reverse transcriptases, called Drt3a, takes a typical route of DNA synthesis; it uses the chunk of non-coding RNA, which consists of the sequence ACACAC, as a template to create a single strand of DNA with repeating Ts and G. It’s the other, Drt3b, that’s thrown up a pretty significant surprise.
Nestled within its active site – the bit of an enzyme where the reaction it’s helping along takes place – is a set of amino acids that mimic RNA. It’s this that Drt3b uses as a template for making new DNA, resulting in a single strand of As and Cs that’s complementary to the strand made by Drt3a, and upending the idea that it can only be nucleic acids like DNA and RNA that can serve as a guide.
“The protein itself serves as the blueprint for the DNA sequence,” senior author Alex Gao told Science. “That was quite a surprise,” he said, adding, “This is a fundamentally new way that life produces DNA.”
What remains unclear is exactly how this unique system helps bacteria to defend themselves from phages. Gao and the team suggest it could be acting like a “molecular sponge” of sorts, holding onto components of the phage that either trigger an immune response from the bacteria it’s attempting to infect, or render the phage functionless.
Regardless, this is one discovery that has yet again taught us that the “rules” of biology aren’t always as set in stone as they might seem.
The study is published in Science.
