Scientists found that pseudouridine helps small RNAs pass on traits and avoid immune detection, offering clues for future RNA-based treatments and how the body tells “self” from “nonself.”
Not everything inside us is, strictly speaking, part of us. The closer we examine the genome, the more we come to appreciate the role of small RNAs in what’s known as epigenetic inheritance, when traits are passed down without changes to the underlying DNA sequence. We now understand that small RNAs help guide epigenetic modifications in both plants and animals.
We also know that pseudouridine (Ψ) is the most common RNA modification. What we haven’t yet done is connect these two important pieces of knowledge. How does Ψ function in small RNAs? Could it play a role in guiding epigenetic inheritance?
Researchers at Cold Spring Harbor Laboratory (CSHL) now have answers to both questions. Their discoveries could help unravel one of biology’s biggest mysteries—how our bodies distinguish “self” from “nonself”—and may open the door to new strategies for defending against viruses in both plants and animals.
To get answers, CSHL Professor and HHMI Investigator Rob Martienssen’s lab collaborated with molecular biologist Tony Kouzarides at the University of Cambridge. Together, they developed a series of screens to scan for Ψ in small RNAs. They found that Ψ does in fact guide epigenetic inheritance. It does so by helping to transport small RNAs into reproductive cells. Amazingly, they found this holds true in plants and mammals. They saw that sperm cells in mice are loaded with Ψ. So too is pollen from the mustard plant Arabidopsis.
From Pseudouridine to Seedless Fruits
Furthermore, the team discovered that Ψ enables a process called the triploid block, whereby plants produce only sterile offspring. Discovered at CSHL nearly 100 years ago, triploid blocks are now found in produce aisles worldwide.
“Seedless cucumbers, seedless melons, seedless fruits—they’re all made this way,” explains Martienssen.
This process is one example of what geneticists call selfish inheritance. Martienssen recently showed that another kind of selfish inheritance, known as gene drive, may have been behind corn’s rapid spread across the Americas. “The same class of small RNAs is responsible for both forms of selfish inheritance,” Martienssen adds.
The question now becomes why are these small RNAs so heavily modified in both plants and animals? One possibility is that these modifications block the immune system from detecting the small RNAs, so they’re recognized as “self” rather than “nonself.” If proven, this hypothesis could help usher in a new generation of RNA therapeutics.
“It would add to our understanding of how RNA vaccines are tolerated by patients, ” says Martienssen.
The more we understand how our bodies distinguish what’s “us” from what isn’t, the better we can fight back against the viruses that threaten humans today as well as those that may do so in the future.
Funding: Howard Hughes Medical Institute, National Institutes of Health, National Science Foundation Plant Genome Research Program, Robertson Research Foundation, Cancer Research UK, Wellcome Trust, Kay Kendall Leukemia Fund, Polish National Science Center
Never miss a breakthrough: Join the SciTechDaily newsletter.
Follow us on Google and Google News.
1 Comment
Karikó published this effect of pseudouridine and other RNA modifications in 2005 (and got nobel prize for it in 2023) and it ia strategy commonly used in RNA vaccines