Shapiro redux: new bacterial editing system (Introduction)

by David Turell , Saturday, August 10, 2024, 19:13 (103 days ago) @ David Turell

Creates loops of DNA:

https://www.sciencedaily.com/releases/2024/08/240809135927.htm

"Since the genetic code was first deciphered in the 1960s, our genes seemed like an open book. By reading and decoding our chromosomes as linear strings of letters, like sentences in a novel, we can identify the genes in our genome and learn why changes in a gene's code affect health.

"This linear rule of life was thought to govern all forms of life -- from humans down to bacteria.

But a new study by Columbia researchers shows that bacteria break that rule and can create free-floating and ephemeral genes, raising the possibility that similar genes exist outside of our own genome.

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"'We now know that, at least in bacteria, there can be other instructions not preserved in the genome that are nonetheless essential for cell survival."

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"The bacterial defense system Sternberg and Tang picked to explore is an odd one: The system involves a piece of RNA with unknown function and a reverse transcriptase, an enzyme that synthesizes DNA from an RNA template. The most common defense systems in bacteria cut or degrade incoming viral DNA, "so we were puzzled by the idea of defending the genome by DNA synthesis," Tang says.

"To learn how the odd defense works, Tang first created a new technique to identify the DNA produced by the reverse transcriptase. The DNA he found was long but repetitive, containing multiple copies of a short sequence within the defense system's RNA molecule.

"He then realized that this portion of the RNA molecule folds into a loop, and the reverse transcriptase travels numerous times around the loop to create the repetitive DNA. "It's like you were intending to photocopy a book, but the copier just started churning out the same page over and over again," Sternberg says.

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"'This is when Stephen did some ingenious digging and found that the DNA molecule is a fully functioning, free-floating, transient gene," Sternberg says.

"The protein coded by this gene, the researchers found, is a critical part of the bacteria's antiviral defense system. Viral infection triggers production of the protein (dubbed Neo by the researchers), which prevents the virus from replicating and infecting neighboring cells.

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"The lab is now using Tang's methods to look for human extrachromosomal genes produced by reverse transcriptases.

"Thousands of reverse transcriptase genes exist in the human genome and many have still undiscovered functions. "There is a significant gap to be filled that might reveal some more interesting biology," Sternberg says.

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"The reverse transcriptase that creates Neo has certain properties that may make it a better option for genome editing in the lab and for creating new gene therapies. And more mysterious reverse transcriptases exist in bacteria that are waiting to be explored.

"'We think bacteria may have a treasure trove of reverse transcriptases that could be opportune starting points for new technologies once we understand how they work," Sternberg says."

Comment: We have evolved from bacteria. They are a good resource for genome research. There are many layers of genome controls yet to be discovered.