Bizarre Bacteria Defy Textbooks by Writing New Genes

The researchers named this sequence neo, for ‘never-ending open reading frame’, because it lacks a sequence that signals the end of a protein and, therefore, theoretically has no limit.

Ewen Callaway in Nature: Genetic information usually travels down a one-way street: genes written in DNA serve as the template for making RNA molecules, which are then translated into proteins. That tidy textbook story got a bit complicated in 1970 when scientists discovered that some viruses have enzymes called reverse transcriptases, which transcribe RNA into DNA — the reverse of the usual traffic flow.

Now, scientists have discovered an even weirder twist1. A bacterial version of reverse transcriptase reads RNA as a template to make completely new genes written in DNA. These genes are then transcribed back into RNA, which is translated into protective proteins when a bacterium is infected by a virus. By contrast, viral reverse transcriptases don’t make new genes; they merely transfer information from RNA to DNA.

“This is crazy molecular biology,” says Aude Bernheim, a bioinformatician at the Pasteur Institute in Paris, who was not involved in the research. “I would have never guessed this type of mechanism existed.”

One-up on CRISPR

Bacteria fend off viruses and other invaders by deploying myriad defences, such as the juggernaut gene-editing system CRISPR. One of the more mysterious defence systems contains the DNA gene for a reverse transcriptase and a short stretch of mysterious RNA without any clear function: the sequence didn’t seem to encode any protein.

To work out how this system works, a team co-led by molecular biologist Stephen Tang and biochemist Samuel Sternberg, both at Columbia University in New York City, searched for the DNA molecules made by a reverse transcriptase from bacteria called Klebsiella pneumoniae. It found very long DNA sequences that consisted of numerous identical repeating segments. Each segment matched a chunk of the mysterious RNA.

Loop-the-loop

To explain this, the authors note that long RNA strands can form hairpin-like shapes, bringing two distant portions close to each other. The researchers found that the K. pneumoniae reverse transcriptase was doing repeated ‘laps’ around the RNA sequence, which was looped over itself like a shoelace, writing the same RNA molecule into DNA many times over. This created a repetitive DNA sequence.

More here.

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