New discovery shows human cells can write RNA sequences into DNA

https://phys.org/news/2021-06-discovery-human-cells-rna-sequences.html

https://www.science.org/doi/10.1126/sciadv.abf1771

Cells contain machinery that duplicates DNA into a new set that goes into a newly formed cell. That same class of machines, called polymerases, also build RNA messages, which are like notes copied from the central DNA repository of recipes, so they can be read more efficiently into proteins. But polymerases were thought to only work in one direction DNA into DNA or RNA. This prevents RNA messages from being rewritten back into the master recipe book of genomic DNA. Now, Thomas Jefferson University researchers provide the first evidence that RNA segments can be written back into DNA, which potentially challenges the central dogma in biology and could have wide implications affecting many fields of biology.

"This work opens the door to many other studies that will help us understand the significance of having a mechanism for converting RNA messages into DNA in our own cells," says Richard Pomerantz, Ph.D., associate professor of biochemistry and molecular biology at Thomas Jefferson University. "The reality that a human polymerase can do this with high efficiency, raises many questions." For example, this finding suggests that RNA messages can be used as templates for repairing or re-writing genomic DNA.

The work was published June 11th in the journal Science Advances.

Together with first author Gurushankar Chandramouly and other collaborators, Dr. Pomerantz's team started by investigating one very unusual polymerase, called polymerase theta. Of the 14 DNA polymerases in mammalian cells, only three do the bulk of the work of duplicating the entire genome to prepare for cell division. The remaining 11 are mostly involved in detecting and making repairs when there's a break or error in the DNA strands. Polymerase theta repairs DNA, but is very error-prone and makes many errors or mutations. The researchers therefore noticed that some of polymerase theta's "bad" qualities were ones it shared with another cellular machine, albeit one more common in viruses—the reverse transcriptase. Like Pol theta, HIV reverse transcriptase acts as a DNA polymerase, but can also bind RNA and read RNA back into a DNA strand.

In a series of elegant experiments, the researchers tested polymerase theta against the reverse transcriptase from HIV, which is one of the best studied of its kind. They showed that polymerase theta was capable of converting RNA messages into DNA, which it did as well as HIV reverse transcriptase, and that it actually did a better job than when duplicating DNA to DNA. Polymerase theta was more efficient and introduced fewer errors when using an RNA template to write new DNA messages, than when duplicating DNA into DNA, suggesting that this function could be its primary purpose in the cell.

The group collaborated with Dr. Xiaojiang S. Chen's lab at USC and used X-ray crystallography to define the structure and found that this molecule was able to change shape in order to accommodate the more bulky RNA molecule—a feat unique among polymerases.

"Our research suggests that polymerase theta's main function is to act as a reverse transcriptase," says Dr. Pomerantz. "In healthy cells, the purpose of this molecule may be toward RNA-mediated DNA repair. In unhealthy cells, such as cancer cells, polymerase theta is highly expressed and promotes cancer cell growth and drug resistance. It will be exciting to further understand how polymerase theta's activity on RNA contributes to DNA repair and cancer-cell proliferation."

They want to modify the RNA of everything.

How Plant 'Vaccines' Could Save Us From a World Without Fruit

https://www.discovermagazine.com/environment/how-plant-vaccines-could-save-us-from-a-world-without-fruit

Researchers are formulating unconventional solutions for tree diseases that harm beloved foods like oranges and chocolate. These include a potential RNA therapy, similar to certain COVID-19 vaccines…

Anne Elizabeth Simon, a virologist at the University of Maryland, is attempting to create what she calls a "vaccine" for crops that could protect our food supply.

Like the current approach to the COVID-19 pandemic, researchers have long dealt with pathogen spread among plants by quarantining infected flora to spare surrounding ones. And, depending on the type of disease, plants may also receive pesticides or antibiotic sprays. But to offer more reliable protection, Simon is part of a team developing a vaccine-like solution as an efficient and relatively quickly deployable solution to preempt — or possibly cure — plant diseases.

This potential fix can’t come fast enough…

Most of these diseases don’t have a simple treatment, and require several costly, time-consuming strategies to mitigate the diseases once they've spread. They can also be difficult to detect because, in some cases, several years pass before symptoms appear. Of course, plant pandemics are no new challenge. In the first half of the 20th century, for instance, a disease caused by fungus killed more than 3 billion American chestnut trees. But overall, climate change, ramped-up global travel and neglect by governments and industry have combined to create a perfect pathogen storm that endangers our food supply. “The time has come to let people know that there are other pandemics going on,” Simon says. “There’s multiple ones happening with trees, and it’s going to lead to a very different world.” The readily available tools can’t always curb encroaching pathogens, as proven by Florida’s quickly spiraling citrus industry — though some claim that regulators and growers worsened conditions by not acting quickly enough.

Citrus trees have already grappled with multiple pathogens over the last few centuries, including the 1800s root rot epidemic and the citrus tristeza virus that cropped up in the 1930s. Most devastating of them all, huanglongbing (HLB) — also commonly called citrus greening — originated in China and has wreaked major havoc over the past two decades.

Where Tree “Vaccines” Come In

Simon joined the fight against plant pathogens by chance: While studying plant RNA viruses in her lab, she happened upon a surprising sample in a genetic sequence database that contradicted her 30 years of research. It turned out to be a new type of virus-like RNA that she named iRNA. It shocked Simon because iRNA lacks certain genes found in all normal plant viruses, yet can still move between cells in a plant’s veins by attaching to plant-generated movement proteins.By tweaking the iRNA to carry tiny fragments of a virus, it can provoke plant enzymes to chop up the harmful virus into little pieces, without causing damage to the plant. “This can be a vehicle, not just for one type of tree, but for many,” Simon says. “It’s all because of this very unusual, never-before-seen property.” The iRNA sample was first discovered by University of California, Riverside researchers in the 1950s when it appeared in limequat trees. They found that the iRNA can infect many citrus species with very mild to zero symptoms. Yet its disease-eradicating properties were only recently discovered when Simon identified the missing genes that allow it to move through plant veins.

“This could become one of the important tools in the belt of the industry and farmers to keep citrus going,” says Georgios Vidalakis, a plant pathologist at the University of California, Riverside, and director of the Citrus Clonal Protection Program. “It looks very promising. Still, there is a lot of work to be done."

Eager to get the ball rolling, Simon founded a company called Silvec Biologics in 2019 and is working to develop a single-step vaccinelike preventative treatment that tricks trees into eradicating not only viruses that cause disease, but also fungi and bacteria — somewhat similar to how mRNA jabs force our immune systems to cook up COVID-19 antibodies. Because the trees containing the original iRNA sample have remained alive for more than 70 years, Simon says it suggests that the vaccine could possibly offer lifetime protection against several pathogens when put into newly planted trees — similar to giving children a standard set of shots. What’s less clear, however, is whether highly degraded trees that have been infected for several years can still benefit from the treatment.

Simon hopes that the iRNA therapy can save infected trees that don’t yet show symptoms of disease.

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Happens.